Prosthetic Metals: Release, Metabolism and Toxicity

The development of metallic joint prostheses has been ongoing for more than a century alongside advancements in hip and knee arthroplasty. Among the materials utilized, the Cobalt-Chromium-Molybdenum (Co-Cr-Mo) and Titanium-Aluminum-Vanadium (Ti-Al-V) alloys are predominant in joint prosthesis construction, predominantly due to their commendable biocompatibility, mechanical strength, and corrosion resistance. Nonetheless, over time, the physical wear, electrochemical corrosion, and inflammation induced by these alloys that occur post-implantation can cause the release of various metallic components. The released metals can then flow and metabolize in vivo, subsequently causing potential local or systemic harm. This review first details jointprosthesis development and acknowledges the release of prosthetic metals. Second, we outline the metallic concentration, biodistribution, and elimination pathways of the released prosthetic metals. Lastly, we discuss the possible organ, cellular, critical biomolecules, and significant signaling pathway toxicities and adverse effects that arise from exposure to these metals.

Zhong, X. Pan, Y. Chen, Q. Lian, J. Gao, Y. Xu, J. Wang, Z. Shi, and H. Cheng,Prosthetic Metals: Release, Metabolism and Toxicity, Int J Nanomedicine, 2024, 19, 5245-5267.

03 Evaluation of colonic anastomosis healing using hybrid nanosheets containing molybdenum disulfide (MoS2) scaffold of human placental amniotic membrane and polycaprolactone (PCL) in rat animal model

Anastomosis is a standard technique following different conditions such as obstruction, tumor, and trauma. Obstruction, adhesion, or anastomosis leakage can be some of its complications. To improve healing and prevent postoperative complications, we design a hybrid scaffold containing acellular human amniotic membranes and polycaprolactone-molybdenum disulfide nanosheets for colon anastomosis. The animal model of colocolonic anastomosis was performed on two groups of rats: control and scaffold. The hybrid scaffold was warped around the anastomosis site in the scaffold group. Samples from the anastomosis site were resected on the third and seventh postoperative days for histopathological and molecular assessments. Histopathologic score and burst pressure had shown significant improvement in the scaffold group. No mortality and anastomosis leakage was reported in the scaffold group. In addition, inflammatory markers were significantly decreased, while anti-inflammatory cytokines were increased in the scaffold group. The result indicates that our hybrid scaffold is a proper choice for colorectal anastomosis repair by declining postoperative complications and accelerating healing.

Ebrahim Soltani, M. Elahi, H. Tashak-Golroudbari, H. Nazari, A. Badripour, A. Heirani-Tabasi, R. Akbari Asbagh, M. A. Dabbagh Ohadi, M. Shabani, M. Sarzaeim, B. Behboudi, M. R. Keramati, A. Kazemeini, and S. M. Ahmadi Tafti,Evaluation of colonic anastomosis healing using hybrid nanosheets containing molybdenum disulfide (_MOS2) scaffold of human placental amniotic membrane and polycaprolactone (PCL) in rat animal model, Naunyn Schmiedebergs Arch Pharmacol, 2023.

Epigallocatechin-3-gallate Mo nanoparticles (EGM NPs) efficiently treat liver injury by strongly reducing oxidative stress, inflammation and endoplasmic reticulum stress

Drug-induced liver injury (DILI) is a serious clinical disease associated with reactive oxygen species (ROS) burst and subsequent inflammatory responses. However, traditional treatments were limited by low efficacy and serious side effects due to the special liver structure. Here, we developed a molybdenum (Mo)-based nanoparticles, EGM NPs, after overall consideration of the pathophysiology of DILI and the advantages of nanodrugs. It demonstrated that EGM NPs treated acetaminophen (APAP)-induced DILI by scavenging ROS and inhibiting inflammation. EGM NPs effectively scavenged various ROS and reduced cell apoptosis at the cellular level. More importantly, EGM NPs can treat APAP-induced DILI in vivo, reducing the levels of liver function indicators in mice with liver injury, scaling down the area of hepatocyte necrosis and successfully inhibiting endoplasmic reticulum (ER) stress in the liver. EGM NPs also showed a certain anti-inflammatory effect by reducing infiltration of macrophages, decreasing pro-inflammatory factors and inhibiting the expression levels of inducible nitric oxide synthase (NOS2) and myeloperoxidase (MPO). Collectively, our findings suggest that EGM NPs-based nanotherapeutic is a novel strategy for the treatment of DILI.

R. Yang, M. Liu, T. J. Zhao, Q. H. Chen, Y. Q. Yang, S. Y. Wang, J. P. Zhang, G. M. Deng, K. W. Sun, Y. Y. Nan, K. Cao, K. L. Ai, and Q. Huang,Epigallocatechin-3-gallate Mo nanoparticles (EGM NPs) efficiently treat liver injury by strongly reducing oxidative stress, inflammation and endoplasmic reticulum stress, Frontiers in Pharmacology, 2022, 13.

MoS₂− Decellularized human amniotic membrane reinforced by MoS₂Polycaprolactone nanofibers, a novel conductive scaffold for cardiac tissue engineering

In order to regenerate myocardial tissues with functional characteristics, we need to copy some properties of the myocardium, such as its extracellular matrix and electrical conductivity. In this study, we synthesized nanosheets of Molybdenum disulfide MoS₂ , and integrated them into polycaprolactone PCL and electrospun on the surface of decellularized human amniotic membrane DHAM with the purpose of improving the scaffolds mechanical properties and electrical conductivity. For in vitro studies, we seeded the mouse embryonic cardiac cells, mouse Embryonic Cardiac Cells mECCs , on the scaffolds and then studied the MoS₂ nanocomposites by scanning electron microscopy and Raman spectroscopy. In addition, we characterized the DHAM/PCL and DHAM/PCL-MoS₂ by SEM, transmission electron microscopy, water contact angle measurement, electrical conductivity, and tensile test. Besides, we confirmed the scaffolds are biocompatible by 3-4, 5-dimethylthiazol^-2-yl ^-2,5^-diphenyl tetrazolium bromide, MTT assay. Furthermore, by means of SEM images, it was shown that mECCs attached to the DHAM/PCL-MoS₂ scaffold have more cell aggregations and elongated morphology. Furthermore, through the Real-Time PCR and immunostaining studies, we found out cardiac genes were maturated and upregulated, and they also included GATA^-4, c-TnT, NKX 2.5, and alpha-myosin heavy chain in cells cultured on DHAM/PCL-MoS₂ scaffold in comparison to DHAM/PCL and DHAM. Therefore, in terms of cardiac tissue engineering, DHAM nanofibrous scaffolds reinforced by PCL-MoS₂ can be suggested as a proper candidate.

H. Nazari, A. Heirani-Tabasi, E. Esmaeili, A. M. Kajbafzadeh, Z. Hassannejad, S. Boroomand, M. H. Shahsavari Alavijeh, M. A. Mishan, S. H. Ahmadi Tafti, M. E. Warkiani, and N. Dadgar,Decellularized human amniotic membrane reinforced by MoS2-Polycaprolactone nanofibers, a novel conductive scaffold for cardiac tissue engineering, J Biomater Appl, 2022, 36, 1527-1539.

MoS₂− Impedimetric detection of miRNA biomarkers using paper-based electrodes modified with bulk crystals or nanosheets of molybdenum disulfide

Paper-based electrodes modified with molybdenum disulfide MoS₂ in the form of bulk crystals or exfoliated nanosheets were developed and used as a biosensing platform for the impedimetric detection of miRNAs miRNA^-155 and miRNA^-21 related to early diagnosis of lung cancer. For this purpose, MoS₂ crystals or nanosheets were used for the modification of the working electrode area of paper-based platform for the first time in this study. The proposed assay offers sensitive and selective detection of microRNAs by electrochemical impedance spectroscopy EIS technique. The entire assay, both the electrode modification and the miRNA detection being completed in 30 min and a single sample droplet 5 μL was enough to cover working electrode area which enabled analysis in low sample volumes. The limits of detection LOD for miRNA^-21 and miRNA^-155 were calculated both in buffer and fetal bovine serum media. It is found that the LOD is varying between 1 and 200 ng/mL. In comparison to nanosheets, a larger electroactive surface area was obtained with bulk MoS₂ resulting in lower LOD values on miRNA detection. The paper-based electrodes showed high specificity towards their target sequences. Moreover, they effectively discriminated single base mismatched non-target sequences. The advantages of these MoS₂ paper based electrodes include high sensitivity, and low-cost provide great potential for improved monitoring of miRNA biomarkers even in artificial serum media.

E. Yarali, E. Eksin, H. Torul, A. Ganguly, U. Tamer, P. Papakonstantinou, and A. Erdem,Impedimetric detection of miRNA biomarkers using paper-based electrodes modified with bulk crystals or nanosheets of molybdenum disulfide, Talanta, 2022, 241, 123233.

MoS₂− Molybdenum disulfide MoS₂ -based nanostructures for tissue engineering applications: prospects and challenges [Review]

Molybdenum disulfide MoS₂ nanostructures have recently earned substantial thoughts from the scientific communities owing to their unique physicochemical, optical and electrical properties. Although MoS₂ has been mostly highlighted for its industrial applications, its biological applicability has not been extensively explored. The introduction of nanotechnology in the field of tissue engineering has significantly contributed to human welfare by displaying advancement in tissue regeneration. Assimilation of MoS₂ nanostructures into the polymer matrix has been considered a persuasive material of choice for futuristic tissue engineering applications. The current review provides a general discussion on the structural properties of different MoS₂ nanostructures. Further, this article focuses on the interactions of MoS₂ with biological systems in terms of its cellular toxicity, and biocompatibility along with its capability for cell proliferation, adhesion, and immunomodulation. The article continues to confer the utility of MoS₂ nanostructure-based scaffolds for various tissue engineering applications. The article also highlights some emerging prospects and possibilities of the applicability of MoS₂ based nanostructures in large organ tissue engineering. Finally, the article concludes with a brief annotation on the challenges and limitations that need to be overcome in order to make plentiful use of this wonderful material for tissue engineering applications.

A. Kumar, A. Sood, and S. S. Han,Molybdenum disulfide MoS₂ -based nanostructures for tissue engineering applications: prospects and challenges, J Mater Chem B, 2022. 2761-2780

In situ detection of plasma exosomal microRNA for lung cancer diagnosis using duplex-specific nuclease and MoS2 nanosheets

MicroRNAs (miRNAs) encapsulated in tumor-derived exosomes are becoming ideal biomarkers for the early diagnosis and prognosis of lung cancer. However, the accuracy and sensitivity are often hampered by the extraction process of exosomal miRNA using traditional methods. Herein, this study developed a fluorogenic quantitative detection method for exosomal miRNA using the fluorescence quenching properties of molybdenum disulfide (MoS2) nanosheets and the enzyme-assisted signal amplification properties of duplex-specific nuclease (DSN). First, a fluorescently-labeled nucleic acid probe was used to hybridize the target miRNA to form a DNA/RNA hybrid structure. Under the action of the DSN, the DNA single strand in the DNA/RNA hybrid strand was selectively digested into smaller oligonucleotide fragments. At the same time, the released miRNA target triggers the next reaction cycle, so as to achieve signal amplification. Then, MoS2 was used to selectively quench the fluorescence of the undigested probe leaving the fluorescent signal of the fluorescently-labeled probe fragments. The fluorometric signals for miRNA-21 had a maximum excitation/emission wavelength of 488/518 nm. Most importantly, the biosensor was then applied for the accurate quantitative detection of miRNA-21 in exosome lysates extracted from human plasma and this method was able to successfully distinguish lung cancer patients from healthy people. This biosensor provides a simple, rapid, and a highly specific quantitative method for exosomal miRNA and has promising potential to be used in the early diagnosis of lung cancer.

Z. B. Gao, H. J. Yuan, Y. H. Mao, L. H. Ding, C. Y. Effah, S. T. He, L. L. He, L. E. Liu, S. C. Yu, Y. L. Wang, J. Wang, Y. M. Tian, F. Yu, H. C. Guo, L. J. Miao, L. B. Qu, and Y. J. Wu,In situ detection of plasma exosomal microRNA for lung cancer diagnosis using duplex-specific nuclease and MoS2 nanosheets, Analyst, 2021, 146, 1924-1931.

Functionalized MoS2Based Nanomaterials for Cancer Phototherapy and Other Biomedical Applications

Transition-metal dichalcogenides (TMDs), as a novel category of nanomaterials and a potential alternate to graphene, are attracting great interest of researchers, because of their strong conductivity, superior catalytic performance, and good optical properties. As the most representative type of all TMDs, molybdenum disulfide (MoS2)-based nanomaterials are expanded into two-dimensional (2D) nanosheets, quantum dots (QDs), flower-like nanoparticles, nanospheres and nanotubes. These types are regarded as promising nanoplatforms for various applications in biomedicine, such as drug delivery, phototherapy, biosensing, bioimaging, theranostics, and antimicrobials, because of the unique planar structures, superb electronic and optical properties (such as thickness-dependent bandgap, strong near-infrared absorbance, and large surface area), and easily functionalized surface sites. Until now, there have been a few reviews about MoS2-based nanomaterials, with regard to functionalization for improvement of properties, such as high drug loading efficiency, dispersibility, physiological stability, biocompatibility, targeting ability, pharmacodynamics, controllable drug release, enhanced treatment and therapeautic efficacy, and even biodegradability and toxicity reduction. Here, we systematically summarized the progress of functionalized MoS2-based nanomaterials with improved physicochemical and biological properties for the biomedical applications. First, we emphatically introduced these biomedical applications in drug delivery, anticancer photothermal therapy (PTT), photodynamic therapy (PDT), and combined phototherapy. Besides, other biomedical applications were also introduced in detail including bioimaging, biosensing, theranostics, toxicity, tissue engineering, and antimicrobials. Lastly, the current challenges, opportunities and prospects of MoS2-based nanomaterials were also discussed in depth. We expect that this review will contribute to a quick and in-depth understanding of the latest progress in bioapplication of MoS2-based nanomaterials, inspiring the creation of various techniques to design and fabricate MoS2-based nanomaterials with multiple capability and high biological safety, and expand them into more application in the field of biomedicine.

M. Liu, H. J. Zhu, Y. Wang, C. Sevencan, and B. L. Li,Functionalized MoS2-Based Nanomaterials for Cancer Phototherapy and Other Biomedical Applications, Acs Materials Letters, 2021, 3, 462-496.

Biosafety, Nontoxic Nanoparticles for VL-NIR Photothermal Therapy Against Oral Squamous Cell Carcinoma

Semiconductor nanocrystals with extraordinary physicochemical and biosafety properties with unique nanostructures have shown tremendous potential as photothermal therapy (PTT) nanosensitizers. Herein, we successfully synthesized chiral molybdenum (Cys-MoO3-x) nanoparticles (NPs) for overcoming the general limitation on electron energy bands and biotoxicity. The obtained Cys-MoO3-x NPs are selected as an ideal design for the treatment of oral squamous cell carcinoma (OSCC) cells through the decoration of cysteine molecules due to excellent initial photothermal spectral analysis of conductivity and light absorbance. Notably, NPs possess the ability to act as visible light (VL) and near-infrared (NIR) double-reactive agents to ablate cancer cells. By combining photoconductive PTT with hypotoxicity biochemotherapy, the treatment validity of OSCC cancer cells can be improved in vitro by up to 89% (808 nm) and get potential PTT effect under VL irradiation, which intuitively proved that the nontoxic NPs were lethally effective for cancer cells under laser irradiation. Hence, this work highlights a powerful and safe NP platform for NIR light-triggered PTT for use in head and neck cancer (HNC) cells, showing promising application prospects in oral tumor treatment.

J. H. Chen, Q. H. Li, F. Wang, M. Yang, L. Xie, and X. Zeng,Biosafety, Nontoxic Nanoparticles for VL-NIR Photothermal Therapy Against Oral Squamous Cell Carcinoma, Acs Omega, 2021, 6, 11240-11247.

MoS2-based nanocomposites for cancer diagnosis and therapy

Molybdenum is a trace dietary element necessary for the survival of humans. Some molybdenum-bearing enzymes are involved in key metabolic activities in the human body (such as xanthine oxidase, aldehyde oxidase and sulfite oxidase). Many molybdenum-based compounds have been widely used in biomedical research. Especially, MoS2-nanomaterials have attracted more attention in cancer diagnosis and treatment recently because of their unique physical and chemical properties. MoS2 can adsorb various biomolecules and drug molecules via covalent or non-covalent interactions because it is easy to modify and possess a high specific surface area, improving its tumor targeting and colloidal stability, as well as accuracy and sensitivity for detecting specific biomarkers. At the same time, in the near-infrared (NIR) window, MoS2 has excellent optical absorption and prominent photothermal conversion efficiency, which can achieve NIR-based phototherapy and NIR-responsive controlled drug-release. Significantly, the modified MoS2-nanocomposite can specifically respond to the tumor microenvironment, leading to drug accumulation in the tumor site increased, reducing its side effects on non-cancerous tissues, and improved therapeutic effect. In this review, we introduced the latest developments of MoS2-nanocomposites in cancer diagnosis and therapy, mainly focusing on biosensors, bioimaging, chemotherapy, phototherapy, microwave hyperthermia, and combination therapy. Furthermore, we also discuss the current challenges and prospects of MoS2-nanocomposites in cancer treatment.

J. Wang, L. Sui, J. Huang, L. Miao, Y. Nie, K. Wang, Z. Yang, Q. Huang, X. Gong, Y. Nan, and K. Ai,MoS2-based nanocomposites for cancer diagnosis and therapy, Bioact Mater, 2021, 6, 4209-4242.

A Mo(VI) based coordination polymer as an antiproliferative agent against cancer cells

Metal ions being an important part of biological systems are of great interest in the designing of new drugs. Molybdenum is an essential trace element for humans, animals, and plants and naturally present in many enzymes hence its complexes can be expected to serve as potential candidates for biomedical applications. A novel molybdenum-based coordination polymer, [Mo-2(mu(2)-O)O-4(2-pyc)(2)(H2O)], is synthesized by a hydrothermal route and structurally characterized by using single crystal X-Ray diffraction. The structure consists of molybdenum octahedra connected by a bridging oxo ligand and 2-pyc forming a one-dimensional coordination polymer. This Mo coordination polymer was found to show a considerable inhibitory effect with IC50 values of 22.63 mu mol L-1, 28.19 mu mol L-1, and 20.97 mu mol L-1, against HepG2 (human liver cancer), A549 (human lung cancer), and MCF-7 (human breast cancer) cell lines respectively. This is the first attempt at exploring the molybdenum-based coordination polymer for antitumor applications. The cell cytotoxicity analysis revealed that the anti-tumor potential of the compound is governed by arresting of the A549, HepG2, and MCF-7 cancer cells in the S phase of the cell cycle. UV-Visible absorption spectroscopy further revealed the binding interaction between the Mo coordination polymer and ctDNA and the binding constant was found to be 5.9 x 10(3) L mol(-1), which is in agreement with those of well-known groove binders. This binding interaction in turn induces apoptosis and necrosis pathways leading to the death of the cancer cells.

A. Joshi, R. Gupta, D. Sharma, and M. Singh,A Mo(VI) based coordination polymer as an antiproliferative agent against cancer cells, Dalton Transactions, 2021, 50, 1253-1260.

In situ detection of plasma exosomal microRNA for lung cancer diagnosis using duplex-specific nuclease and MoS2 nanosheets

Functionalized MoS2Based Nanomaterials for Cancer Phototherapy and Other Biomedical Applications

M. Liu, H. J. Zhu, Y. Wang, C. Sevencan, and B. L. Li,Functionalized MoS2-Based Nanomaterials for Cancer Phototherapy and Other Biomedical Applications, Acs Materials Letters, 2021, 3, 462-496.

Biosafety, Nontoxic Nanoparticles for VL-NIR Photothermal Therapy Against Oral Squamous Cell Carcinoma

J. H. Chen, Q. H. Li, F. Wang, M. Yang, L. Xie, and X. Zeng,Biosafety, Nontoxic Nanoparticles for VL-NIR Photothermal Therapy Against Oral Squamous Cell Carcinoma, Acs Omega, 2021, 6, 11240-11247.

MoS2-based nanocomposites for cancer diagnosis and therapy

J. Wang, L. Sui, J. Huang, L. Miao, Y. Nie, K. Wang, Z. Yang, Q. Huang, X. Gong, Y. Nan, and K. Ai,MoS2-based nanocomposites for cancer diagnosis and therapy, Bioact Mater, 2021, 6, 4209-4242.

A Mo(VI) based coordination polymer as an antiproliferative agent against cancer cells

A. Joshi, R. Gupta, D. Sharma, and M. Singh,A Mo(VI) based coordination polymer as an antiproliferative agent against cancer cells, Dalton Transactions, 2021, 50, 1253-1260.

Preparation of cerium molybdates and their antiviral activity against bacteriophage Phi 6 and SARS-CoV-2

Two cerium molybdates (Ce2Mo3O12 and gamma-Ce2Mo3O13) were prepared using either polymerizable complex method or hydrothermal process. The obtained powders were almost single-phase with different cerium valence. Both samples were found to have antiviral activity against bacteriophage Phi 6. Especially, gamma-Ce2Mo3O13 exhibited high antiviral activity against both bacteriophage Phi 6 and SARS-CoV-2 coronavirus, which causes COVID-19. A synergetic effect of Ce and molybdate ion was inferred along with the specific surface area as key factors for antiviral activity. (C) 2021 The Author(s). Published by Elsevier B.V.

T. Ito, K. Sunada, T. Nagai, H. Ishiguro, R. Nakano, Y. Suzuki, A. Nakano, H. Yano, T. Isobe, S. Matsushita, and A. Nakajima,Preparation of cerium molybdates and their antiviral activity against bacteriophage Phi 6 and SARS-CoV-2, Materials Letters, 2021, 290.

Nanomaterials-Based Biosensors for COVID-19 Detection-A Review

This review paper discusses the properties of nanomaterials, namely graphene, molybdenum disulfide, carbon nanotubes, and quantum dots for unique sensing applications. Based on the specific analyte to be detected and the functionalization techniques that are employed, some noteworthy sensors that have been developed are discussed. Further, biocompatible sensors fabricated from these materials capable of detecting specific chemical compounds are also highlighted for COVID-19 detection purposes, which can aid in efficient and reliable sensing as well as timely diagnosis.

S. Sharma, S. Saini, M. Khangembam, and V. Singh,Nanomaterials-Based Biosensors for COVID-19 Detection-A Review, Ieee Sensors Journal, 2021, 21, 5598-5611.

Molybdenum-based hetero-nanocomposites for cancer therapy, diagnosis and biosensing application: Current advancement and future breakthroughs

In recent years, there have been significant advancements in the nanotechnology for cancer therapy. Even though molybdenum disulphide (MoS2)-based nanocomposites demonstrated extensive applications in biosensing, bioimaging, phototherapy, the review article focusing on MoS2 nanocomposite platform has not been accounted for yet. The review summarizes recent strategies on design and fabrication of MoS2-based nanocomposites and their modulated properties in cancer treatment. The review also discussed several therapeutic strategies (photothermal, photodynamic, immunotherapy, gene therapy and chemotherapy) and their combinations for efficient cancer therapy along with certain case studies. The review also inculcates various diagnostic techniques viz. magnetic resonance imaging, computed tomography, photoacoustic imaging and fluorescence imaging for diagnosis of cancer.

N. Dhas, R. Kudarha, A. Garkal, V. Ghate, S. Sharma, P. Panzade, S. Khot, P. Chaudhari, A. Singh, M. Paryani, S. Lewis, N. Garg, N. Singh, P. Bangar, and T. Mehta,Molybdenum-based hetero-nanocomposites for cancer therapy, diagnosis and biosensing application: Current advancement and future breakthroughs, Journal of Controlled Release, 2021, 330, 257-283.

A water-soluble octahedral molybdenum cluster complex as a potential agent for X-ray induced photodynamic therapy

X-ray-induced photodynamic therapy (X-PDT) has recently evolved into a suitable modality to fight cancer. This technique, which exploits radiosensitizers producing reactive oxygen species, allows for a reduction of the radiation dose needed to eradicate cancer in the frame of the radiotherapy treatment of deep tumors. The use of transition metal complexes able to directly produce singlet oxygen, O2((1)Δ(g)), upon X-ray irradiation constitutes a promising route towards the optimization of the radiosensitizer's architecture. In our endeavour to conceive pertinent agents for X-PDT, we designed an octahedral molybdenum cluster complex (Mo(6)) with iodine inner ligands, and carboxylated apical ligands bearing ethylene oxide organic functions. The sodium salt of this complex is highly soluble in aqueous media and displays red luminescence which is efficiently quenched by oxygen to produce O2((1)Δ(g)) in a high quantum yield. Furthermore, due to its high radiodensity, the complex exhibits radioluminescence in aqueous media, with the same spectral features as for photoluminescence, indicating the production of O2((1)Δ(g)) upon X-ray irradiation. The uptake of the complex by Hep-2 and MRC-5 cells is negligible during the first hours of incubation, then considerably increases in connection with the hydrolysis of the apical ligands. The complex exhibits low toxicity in vitro and induces a radiotoxic effect, noticeable against cancerous Hep-2 cells but negligible against normal MRC-5 cells, at X-ray doses that do not affect cell viability otherwise. The first evaluation of in vivo toxicity of an Mo(6) complex on a mouse model evidences a moderate and delayed toxic effect on kidneys, with an intravenous LD(50) value of 390 ± 30 mg kg(-1), possibly connected with hydrolysis-induced aggregation of the complex. Overall, this complex displays attractive features as a singlet oxygen radiosensitizer for X-PDT, highlighting the potential of transition metal cluster complexes towards this modality.

K. Kirakci, T. N. Pozmogova, A. Y. Protasevich, G. D. Vavilov, D. V. Stass, M. A. Shestopalov, and K. Lang,A water-soluble octahedral molybdenum cluster complex as a potential agent for X-ray induced photodynamic therapy, Biomater Sci, 2021, 9, 2893-2902.

MoS₂-based nanocomposites for cancer diagnosis and therapy

Molybdenum is a trace dietary element necessary for the survival of humans. Some molybdenum-bearing enzymes are involved in key metabolic activities in the human body such as xanthine oxidase, aldehyde oxidase and sulfite oxidase. Many molybdenum-based compounds have been widely used in biomedical research. Especially, MoS^2-nanomaterials have attracted more attention in cancer diagnosis and treatment recently because of their unique physical and chemical properties. MoS₂ can adsorb various biomolecules and drug molecules via covalent or non-covalent interactions because it is easy to modify and possess a high specific surface area, improving its tumor targeting and colloidal stability, as well as accuracy and sensitivity for detecting specific biomarkers. At the same time, in the near-infrared NIR window, MoS₂ has excellent optical absorption and prominent photothermal conversion efficiency, which can achieve NIR-based phototherapy and NIR-responsive controlled drug-release. Significantly, the modified MoS^2-nanocomposite can specifically respond to the tumor microenvironment, leading to drug accumulation in the tumor site increased, reducing its side effects on non-cancerous tissues, and improved therapeutic effect. In this review, we introduced the latest developments of MoS^2-nanocomposites in cancer diagnosis and therapy, mainly focusing on biosensors, bioimaging, chemotherapy, phototherapy, microwave hyperthermia, and combination therapy. Furthermore, we also discuss the current challenges and prospects of MoS^2-nanocomposites in cancer treatment.

J. Wang, L. Sui, J. Huang, L. Miao, Y. Nie, K. Wang, Z. Yang, Q. Huang, X. Gong, Y. Nan, and K. Ai,MoS_2^-based nanocomposites for cancer diagnosis and therapy, Bioact Mater, 2021, 6, 4209-4242.

Mechanistic insights into the treatment of iron-deficiency anemia and arthritis in humans with dietary molybdenum

In the last few decades, there has been a resurgence in interest in the use of dietary supplements to treat diseases in humans and molybdenum has the potential to be used therapeutically. In humans, dietary molybdenum has been shown to treat iron-deficiency anemia and it may treat joint pain in arthritis. It has been proposed that the anti-anemic and tentative anti-arthritic properties of molybdenum are because it is increasing the activity of one or more mammalian molybdoenzymes. Molybdenum forms part of the active site of these enzymes. Despite this, it is unlikely that a molybdenum deficiency can develop in humans that are on an oral diet and not exposed to unsafe levels of a molybdenum antagonist. Therefore, the underlying mechanism by which dietary molybdenum treats or may treat these diseases is currently not known. This minireview examines three possible underlying mechanisms. It investigates the possibility that molybdenum: increases the quantity of active mammalian molybdoenzymes, restores or partially restores activity to malfunctioning mammalian molybdoenzymes, or blocks nuclear receptors, in cells. The examination of these mechanisms has provided an impression of the mechanism by which molybdenum treats iron-deficiency anemia and may treat arthritis; and hypothesize uses of molybdenum for other human diseases.

B. J. Grech,Mechanistic insights into the treatment of iron-deficiency anemia and arthritis in humans with dietary molybdenum, Eur J Clin Nutr, 2021, 75, 1170-1175.

Molybdenum trioxide enhances viability, osteogenic differentiation and extracellular matrix formation of human bone marrow-derived mesenchymal stromal cells

BACKGROUND: Metals and their ions allow specific modifications of the biological properties of bioactive materials that are intended for application in bone tissue engineering. While there is some evidence about the impact of particles derived from orthopedic Cobalt-Chromium-Molybdenum (Co-Cr-Mo) alloys on cells, there is only limited data regarding the influence of the essential trace element Mo and its ions on the viability, osteogenic differentiation as well as on the formation and maturation of the primitive extracellular matrix (ECM) of primary human bone marrow-derived stromal cells (BMSCs) available so far. METHODS: In this study, the influence of a wide range of molybdenum (VI) trioxide (MoO₃), concentrations on BMSC viability was evaluated via measurement of fluorescein diacetate metabolization. Thereafter, the impact of three non-cytotoxic concentrations of MoO₃ on the cellular osteogenic differentiation as well as on ECM formation and maturation of BMSCs was assessed. RESULTS: MoO₃ had no negative influence on BMSC viability in most tested concentrations, as viability was in fact even enhanced. Only the highest concentration (10 mM) of MoO₃ showed cytotoxic effects. Cellular osteogenic differentiation, measured via the marker enzyme alkaline phosphatase was enhanced by the presence of MoO₃ in a concentration-dependent manner. Furthermore, MoO₃ showed a positive influence on the expression of relevant marker genes for osteogenic differentiation (osteopontin, osteocalcin and type I collagen alpha 1) and on the formation and maturation of the primitive ECM, as measured by collagen deposition and ECM calcification. CONCLUSION: MoO₃ is considered as an attractive candidate for supplementation in biomaterials and qualifies for further research.

S. Decker, E. Kunisch, A. Moghaddam, T. Renkawitz, and F. Westhauser,Molybdenum trioxide enhances viability, osteogenic differentiation and extracellular matrix formation of human bone marrow-derived mesenchymal stromal cells, J Trace Elem Med Biol, 2021, 68, 126827.

A Smart Nanoplatform with Photothermal Antibacterial Capability and Antioxidant Activity for Chronic Wound Healing

Chronic wounds, such as the diabetic ulcer wounds have serious effect on people's lives, and can even lead to death. Diabetic ulcer wounds are different from normal wounds and much easier to be infected and induce oxidative stress due to the special surrounding microenvironment, which makes it necessary to prepare materials with antibacterial property and antioxidant activity simultaneously. The molybdenum disulfide-ceria (MoS2 -CeO2 ) nanocomposite possesses both the photo-thermal therapy (PTT) antibacterial capability of polyethylene glycol modified molybdenum disulfide nanosheets and the antioxidant activity of cerium dioxide nanoparticles (CeO2 NPs). By combining the inherent antibacterial activity of CeO2 NPs, the MoS2 -CeO2 nanocomposite exhibits excellent PTT antibacterial capability against both gram-positive and gram-negative bacteria through 808 nm laser treatment, thereby reducing the risk of wound infection. Owing to the abundant oxygen vacancies in CeO2 NPs, Ce3+ and Ce4+ can transform reversibly which endows MoS2 -CeO2 nanocomposite with remarkable antioxidant ability to clear away the excessive reactive oxygen species around the diabetic ulcer wounds and promote wound healing. The results demonstrate that MoS2 -CeO2 nanocomposite is a promising class for the clinical treatment of chronic wounds especially the diabetic ulcer wounds, and 808 nm laser can be used as a PTT antibacterial switch.

T. Ma, X. Zhai, Y. Huang, M. Zhang, X. Zhao, Y. Du, and C. Yan,A Smart Nanoplatform with Photothermal Antibacterial Capability and Antioxidant Activity for Chronic Wound Healing, Adv Healthc Mater, 2021, e2100033.

The antibacterial activities of MoS2 nanosheets towards multi-drug resistant bacteria

We demonstrated that molybdenum disulfide (MoS2) nanosheets can be an excellent solar disinfection agent for multi-drug resistant (MDR) bacteria with disinfection efficiencies >99.9999% in only 30 min. Distinct from other reactive oxygen species (ROS)-dependent photocatalysts, both ROS generation and size decrease contributed to the high antibacterial efficiencies of MoS2

Y. Zhao, Y. Jia, J. Xu, L. Han, F. He, and X. Jiang,The antibacterial activities of MoS(2) nanosheets towards multi-drug resistant bacteria, Chem Commun (Camb), 2021, 57, 2998-3001.

A novel electrochemical lung cancer biomarker cytokeratin 19 fragment antigen 21-1 immunosensor based on Si3N4/MoS2 incorporated MWCNTs and core-shell type magnetic nanoparticles

Lung cancer is one of deadliest and most life threatening cancer types. Cytokeratin 19 fragment antigen 21-1 (CYFRA 21-1) is a significant biomarker for the diagnosis of non-small cell lung cancer (NSCLC). Due to these reasons, a novel electrochemical immunosensor based on a silicon nitride (Si3N4)-molybdenum disulfide (MoS2) composite on multi-walled carbon nanotubes (Si3N4/MoS2-MWCNTs) as an electrochemical sensor platform and core-shell type magnetic mesoporous silica nanoparticles@gold nanoparticles (MMSNs@AuNPs) as a signal amplifier was presented for CYFRA21-1 detection in this study. Capture antibody (Ab(1)) immobilization on a Si3N4/MoS2-MWCNT modified glassy carbon electrode (Si3N4/MoS2-MWCNTs/GCE) was firstly successfully performed by stable electrostatic/ionic interactions between the -NH2 groups of the capture antibody and the polar groups of Si3N4/MoS2. Then, specific antibody-antigen interactions between the electrochemical sensor platform and the signal amplifier formed a novel voltammetric CYFRA21-1 immunosensor. The prepared composite materials and electrochemical sensor surfaces were characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). A linearity range of 0.01-1.0 pg mL(-1) and a low detection limit (LOD) of 2.00 fg mL(-1) were also obtained for analytical applications. Thus, the proposed immunosensor based on Si3N4/MoS2-MWCNTs and MMSNs@AuNPs has great potential for medical diagnosis of lung cancer.

M. L. Yola, N. Atar, and N. Ozcan,A novel electrochemical lung cancer biomarker cytokeratin 19 fragment antigen 21-1 immunosensor based on Si3N4/MoS2 incorporated MWCNTs and core-shell type magnetic nanoparticles, Nanoscale, 2021, 13, 4660-4669.

Targeted Bioimaging of Cancer Cells Using Free Folic Acid-Sensitive Molybdenum Disulfide Quantum Dots through Fluorescence "Turn-Off"

In the present study, a proficient way for targeted bioimaging of folate receptor (FR)-positive cancer cells using free folic acid (FA)- and MoS2 QD-based nanoprobes is discussed along with its advantages over the preparation of orthodox direct FA-nanoprobe bioconjugates for the imaging. The water-soluble MoS2 QDs of size 4-5 nm with cysteine functionalization are synthesized by a simplistic bottom-up hydrothermal method. The as-prepared MoS2 QDs exhibit the blue emission with the highest emission intensity at 444 nm upon excitation of 370 nm. The MoS2 QDs are too sensitive toward FA to produce an effective and stable nanofiber structure through supramolecular interaction, which demonstrates similar to 97% quenching of fluorescence. Moreover, the high selectivity and sensitivity of MoS2 QDs toward FA make the MoS2 QD-based nanoprobe an appropriate candidate for FA-targeted "turn-off" imaging probes for in vivo study of FA-pretreated FR-overexpressed cancer cells. It is obvious from the confocal microscopy images that the FA-pretreated B16F10 cancer cells show higher population of dimmed fluorescence compared to untreated cancer cells and HEK-293 normal cells. The flow cytometry study quantitatively reveals the significant difference of the geometric mean of fluorescence between FA-pretreated and untreated B16F10 cancer cells. Hence, these MoS2 QD-based nanoprobes can be applied as potential nanoprobes for the prediagnosis of cancer through targeted bioimaging.

S. Roy, Y. Bobde, B. Ghosh, and C. Chakraborty,Targeted Bioimaging of Cancer Cells Using Free Folic Acid-Sensitive Molybdenum Disulfide Quantum Dots through Fluorescence "Turn-Off", Acs Applied Bio Materials, 2021, 4, 2839-2849.

Eradication of Fungi Using MoSe₂/Chitosan Nanosheets

Antifungal drug resistance is an increasingly significant threat to humans, livestock, and crops. Recent studies have shown nanomaterials as promising alternatives in combating drug-resistant pathogens. Here, we show that molybdenum diselenide (MoSe₂ nanosheets dispersed in the cationic polymer chitosan (CS exhibit exceptional antifungal activity. The MoSe₂/CS nanosheets provide minimum inhibitory concentrations (MICs between 0.78 and 37.5 mu g ml(^-1 against a variety of unicellular fungal strains and demonstrate minimum fungicidal concentrations (MFCs from 0.5 to 75 mu g ml(^-1 for diverse unicellular and filamentous strains. Furthermore, we demonstrate the ability of MoSe₂/CS to eradicate increasingly prevalent and highly multi-drug-resistant (MDR fungi Candida auris strains with MICs of 25 to 50 mu g ml(^-1 and MFCs of 37.5 to 150 mu g ml(^-1. The effective antifungal activity of MoSe₂/CS was observed after an incubation time of 3 h, which is faster than the time needed for other nanomaterial-based antifungal agents incorporating graphene, two-dimensional (2D nanomaterials, or silver nanoparticles. MoSe₂/CS also showed high biocompatibility and was benign toward human red blood cells and human embryonic kidney cells. Electron microscopy and confocal optical microscopy show that fungal cells treated with MoSe₂/CS nanosheets exhibit morphological deformities, ruptured cell walls and interior voids, and metabolic inactivation. Mechanistic investigations revealed that treatment with MoSe₂/CS triggers complete membrane depolarization and membrane disintegration within 3 h. Hence, this work demonstrates that the biocompatible nanomaterial MoSe₂/CS is a highly effective alternative antifungal agent against many kinds of pathogenic fungi including MDR strains.

S. Saha, M. S. Gilliam, Q. H. Wang, and A. A. Green,Eradication of Fungi Using MoSe₂/Chitosan Nanosheets, ACS Appl. Nano Mater. 2022, 5, 1, 133–148

Two-dimensional material-based virus detection

Cost-effective, rapid, and accurate virus detection technologies play key roles in reducing viral transmission. Prompt and accurate virus detection enables timely treatment and effective quarantine of virus carrier, and therefore effectively reduces the possibility of large-scale spread. However, conventional virus detection techniques often suffer from slow response, high cost or sophisticated procedures. Recently, two-dimensional (2D materials have been used as promising sensing platforms for the high-performance detection of a variety of chemical and biological substances. The unique properties of 2D materials, such as large specific area, active surface interaction with biomolecules and facile surface functionalization, provide advantages in developing novel virus detection technologies with fast response and high sensitivity. Furthermore, 2D materials possess versatile and tunable electronic, electrochemical and optical properties, making them ideal platforms to demonstrate conceptual sensing techniques and explore complex sensing mechanisms in next-generation biosensors. In this review, we first briefly summarize the virus detection techniques with an emphasis on the current efforts in fighting again COVID-19. Then, we introduce the preparation methods and properties of 2D materials utilized in biosensors, including graphene, transition metal dichalcogenides (TMDs and other 2D materials. Furthermore, we discuss the working principles of various virus detection technologies based on emerging 2D materials, such as field-effect transistor-based virus detection, electrochemical virus detection, optical virus detection and other virus detection techniques. Then, we elaborate on the essential works in 2D material-based high-performance virus detection. Finally, our perspective on the challenges and future research direction in this field is discussed.

W. B. Wang, W. Zhai, Y. Chen, Q. Y. He, and H. Zhang,Two-dimensional material-based virus detection, Sci. China Chem.65,497–513 (2022). https://doi.org/10.1007/s11426-021-1150-7

Highly sensitive detection of multiple proteins from single cells by MoS₂-FET biosensors

Single-cell analysis of proteins is critical to gain precise information regarding the mechanisms that dictate the heterogeneity in cellular phenotypes and their differential response to internal and external stimuli. However, tools that allow sensitive and easy measurement of proteins in individual cells are still limited. The emerging semiconductor-based bioelectronics may provide a new approach to overcome the challenges in this field, however its utility in single-cell protein analysis has not been explored. In this study, we investigated multiple protein detection in single cells by MoS₂field effect transistors (MoS₂-FETs modified with specific biological probes. First, β-actin antibody was connected to the surface of MoS₂-FETs by covalent bonds, and the fabricated device was tested using β-actin solution with concentrations from 10(-9 to 10(-3 μg/μL. Next, we examined the application of MoS₂-FET for protein analysis in complex biological samples, and the device showed electrical signal response to human embryonic kidney cell line HEK293T in a dose-dependent manner. Furthermore, we applied this method to analyze individual liver cancer MHCC-97L cells, targeting four cellular proteins, including β-actin, epidermal growth factor receptor, sirtuin-2, and glyceraldehyde-3-phosphate dehydrogenase. The devices modified with corresponding probes could identify the target proteins and showed cell number-dependent responses. As a proof of principle, we demonstrated sensitive and multiplexed detection of proteins in single cells using MoS₂-FETs. The biosensor and this detection method are cost-efficient and user-friendly with broad application prospects in biological studies and clinical diagnosis.

J. Wei, Z. Zhao, K. Lan, Z. Wang, G. Qin, and R. Chen,Highly sensitive detection of multiple proteins from single cells by MoS₂-FET biosensors, Talanta, 2022, 236, 122839.

[Bio-FETs couple a transistor device with a bio-sensitive layer that can specifically detect bio-molecules such as nucleic acids and proteins. https://en.wikipedia.org/wiki/Bio-FET#:~:text=A%20field%2Deffect%20transistor%2Dbased,by%20the%20binding%20of%20molecules.]

Fabrication of MERS-nanovesicle biosensor composed of multi-functional DNA aptamer/graphene- MoS₂nanocomposite based on electrochemical and surface-enhanced Raman spectroscopy

Middle East respiratory syndrome coronavirus (MERS-CoV is one of the most harmful viruses for humans in nowadays. To prevent the spread of MERS-CoV, a valid detection method is highly needed. For the first time, a MERS-nanovesicle (NV biosensor composed of multi-functional DNA aptamer and graphene oxide encapsulated molybdenum disulfide (GO-MoS₂ hybrid nanocomposite was fabricated based on electrochemical (EC and surface-enhanced Raman spectroscopy (SERS techniques. The MERS-NV aptamer was designed for specifically binding to the spike protein on MERS-NVs and it is prepared using the systematic evolution of ligands by exponential enrichment (SELEX technique. For constructing a multi-functional MERS aptamer (MF-aptamer, the prepared aptamer was connected to the DNA 3-way junction (3WJ structure. DNA 3WJ has the three arms that can connect the three individual functional groups including MERS aptamer (bioprobe, methylene blue (signal reporter and thiol group (linker Then, GO-MoS₂hybrid nanocomposite was prepared for the substrate of EC/SERS-based MERS-NV biosensor construction. Then, the assembled multifunctional (MF DNA aptamer was immobilized on GO-MoS₂. The proposed biosensor can detect MERS-NVs not only in a phosphate-buffered saline (PBS solution (SERS LOD: 0.176 pg/ml, EIS LOD: 0.405 pg/ml but also in diluted 10% saliva (SERS LOD: 0.525 pg/ml, EIS LOD: 0.645 pg/ml.

G. Kim, J. Kim, S. M. Kim, T. Kato, J. Yoon, S. Noh, E. Y. Park, C. Park, T. Lee, and J. W. Choi,Fabrication of MERS-nanovesicle biosensor composed of multi-functional DNA aptamer/graphene-MoS₂nanocomposite based on electrochemical and surface-enhanced Raman spectroscopy, Sens Actuators B Chem, 2022, 352, 131060.

Sensory analysis of hepatitis B virus DNA for medicinal clinical diagnostics based on molybdenum doped ZnO nanowires field effect transistor biosensor; a comparative study to PCR test results

In this paper, a bio-sensing setup for investigating hepatitis B virus deoxyribonucleic acid (HBV DNA diagnosis including rapid testing and field effect transistor (FET in label free assay is proposed. The FET biosensor was fabricated by molybdenum doped ZnO nanowires (NWs in easy method and cost-free approach. The materialized NWs were synthesized by physical vapor deposition (PVD growth mechanism. The molybdenum dopant could bring about vacancy sites for DNA adsorption and electric charge transfer. The capability of the fabricated biosensor was evaluated by investigating the PCR-verified samples known as True Positive (TP, True Negative (TN, False Positive (FP and False Negative (FN. The FET biosensor could materialize the clinical tests on samples TP, TN, FP and FN and could distinguish the clinical samples from each other. The designed biosensor showed more precision than the PCR-outcomes by exhibiting more sensitivity on labeled samples known as FN. This research has analytical and comparative study on fabricated biosensor performance. The achieved results show that the biosensor had significant response to samples which have not been carefully detected by PCR test. The fabricated biosensor showed high accuracy, precision, sensitivity, specificity and reproducibility for differentiating (TP, (TN, (FP and (FN samples from healthy and normal sample. The response sensitivity was calculated and biosensor showed a detection limit (LOD of 1 pM. The biosensor demonstrated high response and satisfied signal in the concentration ranges from 1 pM to 10 μM.

M. Shariati, M. Sadeghi, and S. H. R. Shojaei,Sensory analysis of hepatitis B virus DNA for medicinal clinical diagnostics based on molybdenum doped ZnO nanowires field effect transistor biosensor; a comparative study to PCR test results, Anal Chim Acta, 2022, 1195, 339442.

Molybdenum Diphosphide Nanorods with Laser-Potentiated Peroxidase Catalytic/Mild-Photothermal Therapy of Oral Cancer

Chemodynamic therapy (CDT is an emerging treatment that usually employs chemical agents to decompose hydrogen peroxide H₂O₂ into hydroxyl radical •OH via Fenton or Fenton-like reactions, inducing cell apoptosis or necrosis by damaging biomacromolecules such as, lipids, proteins, and DNA. Generally, CDT shows high tumor-specificity and minimal-invasiveness in patients, thus it has attracted extensive research interests. However, the catalytic reaction efficiency of CDT is largely limited by the relatively high pH at the tumor sites. Herein, a 808 nm laser-potentiated peroxidase catalytic/mild-photothermal therapy of molybdenum diphosphide nanorods MoP₂ NRs is developed to improve CDT performance, and simultaneously achieve effective tumor eradication and anti-infection. In this system, MoP₂ NRs exhibit a favorable cytocompatibility due to their inherent excellent elemental biocompatibility. Upon irradiation with an 808 nm laser, MoP₂ NRs act as photosensitizers to efficiently capture the photo-excited band electrons and valance band holes, exhibiting enhanced peroxidase-like catalytic activity to sustainedly decompose tumor endogenous H₂O₂ to •OH, which subsequently destroy the cellular biomacromolecules both in tumor cells and bacteria. As demonstrated both in vitro and in vivo, this system exhibits a superior therapeutic efficiency with inappreciable toxicity. Hence, the work may provide a promising therapeutic technique for further clinical applications.

M. Qian, Z. Cheng, G. Luo, M. Galluzzi, Y. Shen, Z. Li, H. Yang, and X. F. Yu,Molybdenum Diphosphide Nanorods with Laser-Potentiated Peroxidase Catalytic/Mild-Photothermal Therapy of Oral Cancer, Adv Sci (Weinh, 2022, 9, 2101527.

Near-Infrared-Active Copper Molybdenum Sulfide Nanocubes for Phonon-Mediated Clearance of Alzheimer's β-Amyloid Aggregates

Ternary chalcogenide materials have attracted significant interest in recent years because of their unique physicochemical and optoelectronic properties without relying on precious metals, rare earth metals, or toxic elements. Copper molybdenum sulfide (Cu2MoS4, CMS) nanocube is a biocompatible ternary chalcogenide nanomaterial that exhibits near-infrared (NIR) photocatalytic activity based on its low band gap and electron-phonon coupling property. Here, we study the efficacy of CMS nanocubes for dissociating neurotoxic Alzheimer's β-amyloid (Aβ) aggregates under NIR light. The accumulation of Aβ aggregates in the central nervous system is known to cause and exacerbate Alzheimer's disease (AD). However, clearance of the Aβ aggregates from the central nervous system is a considerable challenge due to their robust structure formed through self-assembly via hydrogen bonding and side-chain interactions. Our spectroscopic and microscopic analysis results have demonstrated that NIR-excited CMS nanocubes effectively disassemble Aβ fibrils by changing Aβ fibril's nanoscopic morphology, secondary structure, and primary structure. We have revealed that the toxicity of Aβ fibrils is alleviated by NIR-stimulated CMS nanocubes through in vitro analysis. Moreover, our ex vivo evaluations have suggested that the amount of Aβ plaques in AD mouse's brain decreased significantly by NIR-excited CMS nanocubes without causing any macroscopic damage to the brain tissue. Collectively, this study suggests the potential use of CMS nanocubes as a therapeutic ternary chalcogenide material to alleviate AD in the future.

J. Jang, and C. B. Park,Near-Infrared-Active Copper Molybdenum Sulfide Nanocubes for Phonon-Mediated Clearance of Alzheimer's β-Amyloid Aggregates, ACS Appl Mater Interfaces, 2021, 13, 18581-18593.

VIRUS ANTIVIRAL

Preparation of cerium molybdates and their antiviral activity against bacteriophage Φ6 and SARS-CoV-2

Two cerium molybdates (Ce₂Mo₃O₁₂ and γ-Ce₂Mo₃O₁₃) were prepared using either polymerizable complex method or hydrothermal process. The obtained powders were almost single-phase with different cerium valence. Both samples were found to have antiviral activity against bacteriophage Φ6. Especially, γ-Ce₂Mo₃O₁₃exhibited high antiviral activity against both bacteriophage Φ6 and SARS-CoV-2 coronavirus, which causes COVID-19. A synergetic effect of Ce and molybdate ion was inferred along with the specific surface area as key factors for antiviral activity.

T. Ito, K. Sunada, T. Nagai, H. Ishiguro, R. Nakano, Y. Suzuki, A. Nakano, H. Yano, T. Isobe, S. Matsushita, and A. Nakajima,Preparation of cerium molybdates and their antiviral activity against bacteriophage Φ6 and SARS-CoV-2, Mater Lett, 2021, 290, 129510.

ANEMIA

Mechanistic insights into the treatment of iron-deficiency anemia and arthritis in humans with dietary molybdenum

In the last few decades, there has been a resurgence in interest in the use of dietary supplements to treat diseases in humans and molybdenum has the potential to be used therapeutically. In humans, dietary molybdenum has been shown to treat iron-deficiency anemia and it may treat joint pain in arthritis. It has been proposed that the anti-anemic and tentative anti-arthritic properties of molybdenum are because it is increasing the activity of one or more mammalian molybdoenzymes. Molybdenum forms part of the active site of these enzymes. Despite this, it is unlikely that a molybdenum deficiency can develop in humans that are on an oral diet and not exposed to unsafe levels of a molybdenum antagonist. Therefore, the underlying mechanism by which dietary molybdenum treats or may treat these diseases is currently not known. This minireview examines three possible underlying mechanisms. It investigates the possibility that molybdenum: increases the quantity of active mammalian molybdoenzymes, restores or partially restores activity to malfunctioning mammalian molybdoenzymes, or blocks nuclear receptors, in cells. The examination of these mechanisms has provided an impression of the mechanism by which molybdenum treats iron-deficiency anemia and may treat arthritis; and hypothesize uses of molybdenum for other human diseases.

B. J. Grech,Mechanistic insights into the treatment of iron-deficiency anemia and arthritis in humans with dietary molybdenum, Eur J Clin Nutr, 2021. https://doi.org/10.1038/s41430-020-00845-7.

Two-Dimensional Material-Based Biosensors for Virus Detection

Viral infections are one of the major causes of mortality and economic losses worldwide. Consequently, efficient virus detection methods are crucial to determine the infection prevalence. However, most detection methods face challenges related to false-negative or false-positive results, long response times, high costs, and/or the need for specialized equipment and staff. Such issues can be overcome by access to low-cost and fast response point-of-care detection systems, and two-dimensional materials (2DMs) can play a critical role in this regard. Indeed, the unique and tunable physicochemical properties of 2DMs provide many advantages for developing biosensors for viral infections with high sensitivity and selectivity. Fast, accurate, and reliable detection, even at early infection stages by the virus, can be potentially enabled by highly accessible surface interactions between the 2DMs and the analytes. High selectivity can be obtained by functionalization of the 2DMs with antibodies, nucleic acids, proteins, peptides, or aptamers, allowing for specific binding to a particular virus, viral fingerprints, or proteins released by the host organism. Multiplexed detection and discrimination between different virus strains are also feasible. In this Review, we present a comprehensive overview of the major advances of 2DM-based biosensors for the detection of viruses. We describe the main factors governing the efficient interactions between viruses and 2DMs, making them ideal candidates for the detection of viral infections. We also critically detail their advantages and drawbacks, providing insights for the development of future biosensors for virus detection. Lastly, we provide suggestions to stimulate research in the fast expanding field of 2DMs that could help in designing advanced systems for preventing virus-related pandemics.

C. Ménard-Moyon, A. Bianco, and K. Kalantar-Zadeh,Two-Dimensional Material-Based Biosensors for Virus Detection, ACS Sens, 2020, 5, 3739-3769.

Molybdenum cluster loaded PLGA nanoparticles as efficient tools against epithelial ovarian cancer

In this study, poly (lactic-co-glycolic) acid nanoparticles loading inorganic molybdenum octahedral cluster were used for photodynamic therapy (PDT) of ovarian cancer. Three cluster compounds, ((C₄H₉)₄N)₂(Mo₆Br₈)Br₆ , Cs₂(Mo6Br8)Br6 and Cs₂Mo₆I₈(OOC₂F₅)₆ denoted TMB, CMB and CMIF were studied following their incorporation in nanoparticles by a nanoprecipitation method. All resulting nanoparticles exhibited physico-chemical characteristics such as size and zeta potential compatible with cellular uptake. All cluster compounds tested were shown to produce singlet oxygen in vitro once released from their nanoparticulate system. Confocal images showed an internalisation of cluster loaded nanoparticles (CNPs) in A2780 ovarian cancer cell line, more efficient with CMIF compared to CMB or TMB loaded nanoparticles. In vitro cellular viability studies conducted on A2780 cell line treated with non activated CNPs did not show any sign of toxicity for concentrations up to 15 µM. Following photo-activation, CNPs were able to generate singlet oxygen resulting in a decrease of the cellular viability, compared to non-activated conditions. Nevertheless, no significant differences between IC(50) with or without photo-activation were observed with TMB and CMB CNPs while for CMIF loaded nanoparticles, the photo-activation led to a significant decrease of cellular viability compared to the non activated condition and this decrease was independant of the P/C ratio. The strong photo-toxicity obtained for CMIF loaded nanoparticles with a P/C ratio of 2.5, as shown with half maximal inhibitory concentration (IC(50)) value near 1.8 µM suggests that PLGA nanoparticles seem to be efficient delivery systems intended for tumor management and that CMIF can be further investigated as photosensitizer for PDT of ovarian cancer.

N. Brandhonneur, Y. Boucaud, A. Verger, N. Dumait, Y. Molard, S. Cordier, and G. Dollo,Molybdenum cluster loaded PLGA nanoparticles as efficient tools against epithelial ovarian cancer, Int J Pharm, 2021, 592, 120079.

Combinatorial discovery of Mo-based polyoxometalate clusters for tumor photothermal therapy and normal cell protection

Nanomaterials with multiple functions such as precision diagnosis, therapeutic efficacy and biosafety are attractive for tumor treatment but remain a technical challenge. In this study, molybdenum (Mo)-based polyoxometalate clusters (Mo-POM) with considerable photothermal conversion efficiency (∼56.6%) and high stability (>30 days) were prepared through a modification of the Folin-Ciocalteu method. These synthetic particles accumulated at the target site, and induced thermal ablation of the tumor following near infrared (NIR) absorption. Furthermore, the Mo-POM effectively scavenged reactive oxygen species (ROS) through charge transfer between Mo(VI) and Mo(V) states, thereby avoiding off-target effects on normal cells and improving the therapeutic efficiency both in vitro and in vivo. Therefore, for the first time, we prepared Mo-POM having two key functions, i.e., photothermal therapy (PTT) for cancer cells and protection of normal cells. These exceptional features may open up the exploration of Mo-POM as new tools for PTT against tumors in clinical applications.

W. Zhao, J. Wang, H. Wang, S. Lu, Y. Song, H. Chen, Y. Ma, L. Wang, and T. Sun,Combinatorial discovery of Mo-based polyoxometalate clusters for tumor photothermal therapy and normal cell protection, Biomaterials science, 2020, 8, 6017-6024.

DNA

Electrochemical detection of cell concentration based on reaction of DNA with molybdate

This article describes a fast and simple electrochemical assay for detecting cell concentration. After cell death, the membrane of cells will be broken, and DNA molecules contained in the cells will be released, but this does not happen in living cells. Sodium molybdate can react with the phosphate backbone of the released DNA molecules to form phosphomolybdate precipitation and produces a corresponding redox current. The higher the concentration of DNA, the stronger the intensity of the current generated. Sodium molybdate solution and centrifuged cell supernatant were added onto the glassy carbon electrode to determine the cell concentration by measuring the current intensity. The cell viability, which means the ratio of living cells to the total cells, can also be determined by this method. This assay has the advantages of high sensitivity, low detection limit, and wide detection range. In addition, this method was successfully applied to the detection of cell concentration in human serum, which has potential clinical applications. (C) 2019 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.

W. Z. Zhang, X. X. Jiang, S. P. Liu, D. Zhao, and M. H. Yang, Electrochemical detection of cell concentration based on reaction of DNA with molybdate, Chinese Chemical Letters, 2020, 31, 459-462.

Biological effects of molybdenum compounds in nanosized forms under in vitro and in vivo conditions

Nanoparticles of transition metal dichalcogenides, particularly of molybdenum (Mo), have gained a lot of focus due to their exceptional physicochemical properties and the growing number of technological applications. These nanoparticles are also considered as potential therapeutic tools, biosensors or drug carriers. It is crucial to thoroughly examine their biocompatibility and ensure safe usage. The aim of this review is to analyze the available data on the biological effects of different nanoforms of elemental Mo and its compounds. In the reviewed publications, different conditions were described, including different experimental models, examined nanoforms, and their used concentrations. Due to these differences, the results are rather difficult to compare. Various studies classify Mo related nanomaterials as very toxic, mildly toxic or non-toxic. Similarly, the mechanisms of toxicity proposed in some studies are different, including oxidative stress induction, physical membrane disruption or DNA damage. Quite promising, however, are the potential medical applications of MoS2 nanoparticles in therapy of cancer and Alzheimer's disease. Further studies on biocompatibility of nanomaterials based on Mo compounds are warranted.

Z. Sobanska, L. Zapor, M. Szparaga, and M. Stepnik, Biological effects of molybdenum compounds in nanosized forms under in vitro and in vivo conditions, International Journal of Occupational Medicine and Environmental Health, 2020, 33, 1-19.

CANCER

Layered MoS₂ nanosheets modified by biomimetic phospholipids: Enhanced stability and its synergistic treatment of cancer [therapy] with chemo-photothermal therapy

Cancer is a huge challenge humanity facing today, and single chemical treatments inevitably have shortcomings such as poor selectivity and large side effects. This paper constructed an egg yolk phospholipids modified molybdenum disulfide (MoS₂) nanocarrier system for the treatment of tumors via the combination of chemotherapy and photothermal therapy. The lipid-modified layered MoS₂ (MoS^2-Lipid) nanocomposite was synthesized by simple physical adsorption. The lipid modification strongly enhanced the stability of MoS₂ nanosheets and the nanocarrier has a large drug loading amount with pH dependent DOX release profile, an excellent photothermal property, and an ideal cellular uptake property. Therefore, we combined chemotherapy and photothermal therapy to treat tumors synergistically. Through in vitro cell experiments, pure nanocomposite had no obvious cytotoxicity to cells, and the synergistic treatment of tumors by chemotherapy and photothermal therapy was more effective than any single treatment. More importantly, in vivo experiments indicated that lipid modification enhanced the accumulation of the nanocarrier in mice tumors, thus a better photothermal performance could be seen compared with original MoS₂ nanosheets. In summary, the MoS₂^-lipid nanocomposite is a promising nanocarrier for the treatment of tumors by chemo and photothermal therapy.

M. Xie, N. Yang, J. Cheng, M. Yang, T. Deng, Y. Li, and C. Feng, Layered mos₂ nanosheets modified by biomimetic phospholipids: Enhanced stability and its synergistic treatment of cancer with chemo-photothermal therapy, Colloids Surf B Biointerfaces, 2020, 187, 110631.

Case-control study of brain and other central nervous system cancer among workers at semiconductor and storage device manufacturing facilities

OBJECTIVE: This study evaluated the relationship between brain and other central nervous system cancer ('CNS cancer') and exposures at two semiconductor and electronic module manufacturing facilities and at a storage device manufacturing facility. METHODS: The case-control study, nested in a cohort of 126 836 employees, compared 120 CNS cancer cases and 1028 matched controls with respect to employment in 10 process groups and estimated cumulative exposure to 31 known or possible carcinogens. RESULTS: CNS cancer was associated with module manufacturing operations at two facilities. Module manufacturing is a process that begins with production of ceramic substrates followed by attachment of completed semiconductor chips and metal-containing circuitry resulting in a high performing electronic device. Positive associations with the highest tertile of estimated cumulative exposure were found for several chemicals, including 2-butoxyethanol, cyclohexanone, ortho-dichlorobenzene, cadmium, molybdenum, trichloroethylene and vinyl chloride. CONCLUSIONS: Results suggested positive associations between CNS cancer and specific operations and chemicals experienced in the semiconductor and electronic module manufacturing industry. However, lack of external support for these findings precludes a causal interpretation, and the observed associations may have been due to chance.

E. G. Rodrigues, R. F. Herrick, J. Stewart, H. Palacios, F. Laden, W. Clark, and E. Delzell, Case-control study of brain and other central nervous system cancer among workers at semiconductor and storage device manufacturing facilities, Occup Environ Med, 2020, 77, 238-248.

A Metallomic approach to assess associations of serum metal levels with gallstones and gallbladder cancer

BACKGROUND AND AIMS: Exposure to metals may promote the risk for cancers. We evaluated the associations of a broad spectrum of metals with gallbladder cancer (GBC) and gallstones. APPROACH AND RESULTS: A total of 259 patients with GBC, 701 patients with gallstones, and 851 population-based controls were enrolled in Shanghai, China. A metallome panel was used to simultaneously detect 18 metals in serum through inductively coupled plasma-mass spectrometry. Logistic regression models were used to estimate crude or adjusted odds ratios (ORadj ) with 95% confidence intervals (CIs) for the association between metal levels and gallbladder disease. Among the 18 metals tested, 12 were significantly associated with GBC and six with gallstones (Pcorrected < 0.002). Boron, lithium, molybdenum, and arsenic levels were associated with GBC compared to gallstones as well as with gallstones compared to population-based controls. Elevated levels of cadmium, chromium, copper, molybdenum, and vanadium were positively associated with GBC versus gallstones; and the ORadj for the highest tertile (T3) compared to the lowest tertile (T1) ranged from 1.80 to 7.28, with evidence of dose-response trends (P < 0.05). Arsenic, boron, iron, lithium, magnesium, selenium, and sulfur were inversely associated with GBC, with the T3 versus T1 ORadj ranging from 0.20 to 0.69. Arsenic, boron, calcium, lithium, molybdenum, and phosphorus were negatively associated with gallstones, with the T3 versus T1 ORadj ranging from 0.50 to 0.75 (P < 0.05). CONCLUSIONS: Metals were associated with both GBC and gallstones, providing cross-sectional evidence of association across the natural history of disease. Longitudinal studies are needed to evaluate the temporality of metal exposure and gallbladder diseases and to investigate the mechanisms of disease pathogenesis.

M. H. Lee, Y. T. Gao, Y. H. Huang, E. E. McGee, T. Lam, B. Wang, M. C. Shen, A. Rashid, R. M. Pfeiffer, A. W. Hsing, and J. Koshiol, A metallomic approach to assess associations of serum metal levels with gallstones and gallbladder cancer, Hepatology, 2020, 71, 917-928

.

Steering efficacy of nano molybdenum towards cancer [therapy]: Mechanism of action

Conventional cancer therapies possess a plethora of limitations which led to the awakening of nanotechnology and nanomedicine. However, technological success is widely dependent on complete understanding of the complexity and heterogeneity of tumor biology on one hand and nanobiointeractions associated with challenges of synthesis, translation, and commercialization on the other. The present study therefore deals with one such targeted approach aiming at synthesizing, characterizing, and understanding the efficacy of molybdenum oxide nanoparticles. The phase structure, morphology, and elemental composition of the synthesized nanoparticles were characterized using Fourier transform infrared spectroscopy, Raman spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy, and scanning electron microscopy. The cytotoxicity studies [3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide MTT assay] revealed that the IC50 vales of molybdenum trioxide (MoO3) particles against skin cancer cells (melanoma and non-melanoma) were around 200-300 mug. The nanoparticles were found to induce mitochondrial-mediated apoptosis driven by the apoptotic genes such as BAX and Bcl2. Molybdenum being a cofactor for the majority of metabolic enzymes could have triggered the selective internalization of the nanoparticles which in turn could have modified the granularity of the cytoplasm and subsequently lead to mitochondrial-mediated apoptosis. Further, the anti-angiogenic property of MoO3 nanoparticles was corroborated using Chick chorioallantoic membrane (CAM) assay and aortic ring assay. Taken together , unraveling the role of MoO3 nanoparticles in cancer and angiogenesis opens up venues for nano biological intervention of selective cancer cell targeting with minimal damage to the normal cells using natural trace elements that are generally known to influence various metabolic enzymes.

Conclusion

The synthesized MoO3 nanoparticles exhibit an inherent cytotoxicity towards cancer cells in comparison to normal cells thereby serving as a target. Further, being a nanostructure also provides a scope for functionalizing and application as a targeted carrier for therapeutic agents for off-loading in cancer cells. In conclusion, this paper provides an insight to meet the challenges of controllable and reproducible synthetic strategies as well as facilitate the development of next-generation nanomedicine through incorporation of therapeutic bioactives/drugs reducing the limitations of drug payloads and resistance.

J. Indrakumar, and P. S. Korrapati, Steering efficacy of nano molybdenum towards cancer: Mechanism of action, Biol Trace Elem Res, 2020, 194, 121-134.

[Mitochondrial-mediated apoptosis: Xiong S, Mu T, Wang G, Jiang X. Mitochondria-mediated apoptosis in mammals. Protein Cell. 2014;5(10):737‐749. doi:10.1007/s13238-014-0089-1]

CANCER

Biodegradation-mediated enzymatic activity-tunable molybdenum oxide nanourchins for tumor-specific cascade catalytic therapy

Recent advances in nanomedicine have facilitated the development of potent nanomaterials with intrinsic enzyme-like activities (nanozymes) for cancer therapy. However, it remains a great challenge to fabricate smart nanozymes that precisely perform enzymatic activity in tumor microenvironment without inducing off-target toxicity to surrounding normal tissues. Herein, we report on designed fabrication of biodegradation-medicated enzymatic activity-tunable molybdenum oxide nanourchins (MoO_3-x NUs), which selectively perform therapeutic activity in tumor microenvironment via cascade catalytic reactions, while keeping normal tissues unharmed due to their responsive biodegradation in physiological environment. Specifically, the MoO_3-x NUs first induce catalase (CAT)-like reactivity to decompose hydrogen peroxide (H₂O₂) in tumor microenvironment, producing a considerable amount of O^-₂ for subsequent oxidase (OXD)-like reactivity of MoO₃-x NUs; a substantial cytotoxic superoxide radical (center dot O^-₂(-)) is thus generated for tumor cell apoptosis. Interestingly, once exposed to neutral blood or normal tissues, MoO_3-x NUs rapidly lose the enzymatic activity via pH-responsive biodegradation and are excreted in urine, thus ultimately ensuring safety. The current study demonstrates a proof of concept of biodegradation-medicated in vivo catalytic activity-tunable nanozymes for tumor-specific cascade catalytic therapy with minimal off-target toxicity.

X. Hu, F. Y. Li, F. Xia, X. Guo, N. Wang, L. L. Liang, B. Yang, K. L. Fan, X. Y. Yan, and D. S. Ling, Biodegradation-mediated enzymatic activity-tunable molybdenum oxide nanourchins for tumor-specific cascade catalytic therapy, Journal of the American Chemical Society, 2020, 142, 1636-1644.

CANCER

Biodegradation-Mediated Enzymatic Activity-Tunable Molybdenum Oxide Nanourchins for Tumor-Specific Cascade Catalytic Therapy

Recent advances in nanomedicine have facilitated the development of potent nanomaterials with intrinsic enzyme-like activities (nanozymes) for cancer therapy. However, it remains a great challenge to fabricate smart nanozymes that precisely perform enzymatic activity in tumor microenvironment without inducing off-target toxicity to surrounding normal tissues. Herein, we report on designed fabrication of biodegradation-medicated enzymatic activity-tunable molybdenum oxide nanourchins (MoO₃^-x NUs), which selectively perform therapeutic activity in tumor microenvironment via cascade catalytic reactions, while keeping normal tissues unharmed due to their responsive biodegradation in physiological environment. Specifically, the MoO₃^-x NUs first induce catalase (CAT)-like reactivity to decompose hydrogen peroxide (H₂O₂) in tumor microenvironment, producing a considerable amount of O₂ for subsequent oxidase (OXD)-like reactivity of MoO₃^-x NUs; a substantial cytotoxic superoxide radical (.O₂^-) is thus generated for tumor cell apoptosis. Interestingly, once exposed to neutral blood or normal tissues, MoO₃^-x NUs rapidly lose the enzymatic activity via pH-responsive biodegradation and are excreted in urine, thus ultimately ensuring safety. The current study demonstrates a proof of concept of biodegradation-medicated in vivo catalytic activity-tunable nanozymes for tumor-specific cascade catalytic therapy with minimal off-target toxicity.

X. Hu, F. Li, F. Xia, X. Guo, N. Wang, L. Liang, B. Yang, K. Fan, X. Yan, and D. Ling,Biodegradation-Mediated Enzymatic Activity-Tunable Molybdenum Oxide Nanourchins for Tumor-Specific Cascade Catalytic Therapy, Journal of the American Chemical Society, 2020, 142, 1636-1644.

CANCER

Steering Efficacy of Nano Molybdenum Towards Cancer: Mechanism of Action

Conventional cancer therapies possess a plethora of limitations which led to the awakening of nanotechnology and nanomedicine. However, technological success is widely dependent on complete understanding of the complexity and heterogeneity of tumor biology on one hand and nanobiointeractions associated with challenges of synthesis, translation, and commercialization on the other. The present study therefore deals with one such targeted approach aiming at synthesizing, characterizing, and understanding the efficacy of molybdenum oxide nanoparticles. The phase structure, morphology, and elemental composition of the synthesized nanoparticles were characterized using Fourier transform infrared spectroscopy, Raman spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy, and scanning electron microscopy. The cytotoxicity studies revealed that the IC₅₀ vales of molybdenum trioxide (MoO₃) particles against skin cancer cells (melanoma and non-melanoma) were around 200-300 mug. The nanoparticles were found to induce mitochondrial-mediated apoptosis driven by the apoptotic genes such as BAX and Bcl₂. Molybdenum being a cofactor for the majority of metabolic enzymes could have triggered the selective internalization of the nanoparticles which in turn could have modified the granularity of the cytoplasm and subsequently lead to mitochondrial-mediated apoptosis. Further, the anti-angiogenic property of MoO₃ nanoparticles was corroborated using Chick chorioallantoic membrane (CAM) assay and aortic ring assay. Taken together , unraveling the role of MoO₃ nanoparticles in cancer and angiogenesis opens up venues for nano biological intervention of selective cancer cell targeting with minimal damage to the normal cells using natural trace elements that are generally known to influence various metabolic enzymes.

J. Indrakumar, and P. S. Korrapati,Steering Efficacy of Nano Molybdenum Towards Cancer: Mechanism of Action, Biol Trace Elem Res, 2020, 194, 121-134.

ANTIBACTERIAL

Dual light-induced in situ antibacterial activities of biocompatibleTiO₂/MoS₂/PDA/RGD nanorod arrays on titanium

Prevention of bacterial infection and promotion of osseointegration are two important issues for titanium (Ti) implants in medical research. In addition, after a biofilm is formed on the surface of implants, the immune system and antibiotic therapy may fail. In this work, bio-functionalized titanium dioxide (TiO₂)/molybdenum disulfide (MoS₂)/polydopamine (PDA)/arginine-glycine-aspartic acid (RGD) nanorod arrays (NAs) are prepared on Ti implants to not only kill bacteria noninvasively upon co-irradiation of 660 nm visible light (VL) and 808 nm near infrared (NIR) light, but also promote the osteogenic activity simultaneously. Dual light irradiation triggers the TiO₂/MoS₂ NA to generate hyperthermia and reactive oxygen species (ROS) in 10 min. The synergistic effects of the generated hyperthermia and ROS increase the bacterial membrane permeability and bacteria are killed rapidly and efficiently in vitro and in vivo. The biofilm is also eradicated and RGD on the nanorods improves cell adhesion, proliferation, and osteogenic differentiation. The strategy described here for the design of bio-functionalized coatings on Ti implants has great clinical potential in orthopedics, dentistry, and other medical fields.

G. Zhang, X. Zhang, Y. Yang, R. Chi, J. Shi, R. Hang, X. Huang, X. Yao, P. K. Chu, and X. Zhang,Dual light-induced in situ antibacterial activities of biocompatibleTiO₂/MoS₂/PDA/RGD nanorod arrays on titanium, Biomaterials science, 2019.

Octahedral molybdenum cluster as a photoactive antimicrobial additive to a fluoroplastic

Finding methods that fight bacterial infection or contamination, while minimising our reliance on antibiotics is one of the most pressing needs of this century. Although the utilisation of UV-C light and strong oxidising agents, such as bleach, are still efficacious methods for eliminating bacterial surface contamination, both methods present severe health and/or environmental hazards. Materials with intrinsic photodynamic activity (i.e. a material's ability upon photoexcitation to convert molecular oxygen into reactive oxygen species such as singlet oxygen), which work with light within the visible photomagnetic spectrum could offer a significantly safer alternative. Here we present a new, bespoke molybdenum cluster (Bu₄N)₂[{Mo₆I₈}(CF₃(CF₂)₆COO)₆], which is both efficient in the generation of singlet oxygen upon photoirradiation and compatible with the fluoropolymer (F-32L) known for its good oxygen permeability. Thus, (Bu₄N)₂[{Mo₆I₈}(CF₃(CF₂)₆COO)₆]/F-32L mixtures have been solution-processed to give homogenous films of smooth and fibrous morphologies and which displayed high photoinduced antibacterial activity against four common pathogens under visible light irradiation. These materials thus have potential in applications ranging from antibacterial coatings to filtration membranes and air conditioners to prevent spread of bacterial infections.

N. A. Vorotnikova, A. Y. Alekseev, Y. A. Vorotnikov, D. V. Evtushok, Y. Molard, M. Amela-Cortes, S. Cordier, A. I. Smolentsev, C. G. Burton, P. M. Kozhin, P. Zhu, P. D. Topham, Y. V. Mironov, M. Bradley, O. A. Efremova, and M. A. Shestopalov,Octahedral molybdenum cluster as a photoactive antimicrobial additive to a fluoroplastic, Materials science & engineering. C, Materials for biological applications, 2019, 105, 110150.

Antibacterial activity and cytotoxicity of novel silkworm-like nisin@PEGylated MoS₂

Recently, molybdenum disulfide functionalized with poly-ethylene glycol (PEGylated MoS₂) has been widely used as a new drug delivery vehicle in biomedical field. However, the weak antibacterial activity of PEGylated MoS₂ limits its application as an antibacterial agent. In this work, a novel silkworm-like conjugate of nisin loaded PEGylated MoS₂ (nisin@PEGylated MoS₂) was developed for antibacterial application. The morphology and structure of PEGylated MoS₂ were strongly dependent on the Mo/S molar ratio of precursors during the solvothermal process. The silkworm-like skeleton was well kept after loading with nisin. A high level of reactive oxygen species (ROS) induced by the conjugate was an important cause of bacteria death. Due to the different structure of cell membranes, the sharp edges could more easily puncture into Escherichia coli (E. coli) as compared with Staphylococcus aureus (S. aureus) and produced more intracellular ROS, which improved the antibacterial activity of nisin against E. coli. As a result, nisin@PEGylated MoS₂ displayed the antibacterial activity against both gram-positive and gram-negative bacteria. Furthermore, the toxicity of the conjugate was very low. Therefore, the target conjugate of nisin@PEGylated MoS₂ may have great potential application as an antibacterial agent.

P. Wang, H. Wang, X. Zhao, L. Li, M. Chen, J. Cheng, J. Liu, and X. Li,Antibacterial activity and cytotoxicity of novel silkworm-like nisin@PEGylated MoS₂, Colloids and surfaces. B, Biointerfaces, 2019, 183, 110491.

ALZHEIMER

A disease-modifying treatment for Alzheimer's disease: focus on the trans-sulfuration pathway

High homocysteine levels in Alzheimer's disease (AD) result from low activity of the trans-sulfuration pathway. Glutathione levels are also low in AD. L-cysteine is required for the synthesis of glutathione. The synthesis of coenzyme A (CoA) requires L-cysteine, which is synthesized via the trans-sulfuration pathway. CoA is required for the synthesis of acetylcholine and appropriate cholinergic neurotransmission. L-cysteine is required for the synthesis of molybdenum-containing proteins. Sulfite oxidase (SUOX), which is a molybdenum-containing protein, could be dysregulated in AD. SUOX detoxifies the sulfites. Glutaminergic neurotransmission could be dysregulated in AD due to low levels of SUOX and high levels of sulfites. L-cysteine provides sulfur for iron-sulfur clusters. Oxidative phosphorylation (OXPHOS) is heavily dependent on iron-sulfur proteins. The decrease in OXPHOS seen in AD could be due to dysregulations of the trans-sulfuration pathway. There is a decrease in aconitase 1 (ACO1) in AD. ACO1 is an iron-sulfur enzyme in the citric acid cycle that upon loss of an iron-sulfur cluster converts to iron regulatory protein 1 (IRP1). With the dysregulation of iron-sulfur cluster formation ACO1 will convert to IRP1 which will decrease the 2-oxglutarate synthesis dysregulating the citric acid cycle and also dysregulating iron metabolism. Selenomethionine is also metabolized by the trans-sulfuration pathway. With the low activity of the trans-sulfuration pathway in AD selenoproteins will be dysregulated in AD. Dysregulation of selenoproteins could lead to oxidant stress in AD. In this article, we propose a novel treatment for AD that addresses dysregulations resulting from low activity of the trans-sulfuration pathway and low L-cysteine.

T. Berry, E. Abohamza, and A. A. Moustafa,A disease-modifying treatment for Alzheimer's disease: focus on the trans-sulfuration pathway, Reviews in the neurosciences, 2019.

THERAPEUTIC

MoO₃ CANCER

Steering Efficacy of Nano Molybdenum Towards Cancer: Mechanism of Action

Conventional cancer therapies possess a plethora of limitations which led to the awakening of nanotechnology and nanomedicine. However, technological success is widely dependent on complete understanding of the complexity and heterogeneity of tumor biology on one hand and nanobiointeractions associated with challenges of synthesis, translation, and commercialization on the other. The present study therefore deals with one such targeted approach aiming at synthesizing, characterizing, and understanding the efficacy of molybdenum oxide nanoparticles. The phase structure, morphology, and elemental composition of the synthesized nanoparticles were characterized using Fourier transform infrared spectroscopy, Raman spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy, and scanning electron microscopy. The cytotoxicity studies revealed that the IC₅₀ vales of molybdenum trioxide (MoO₃) particles against skin cancer cells (melanoma and non-melanoma) were around 200-300 mug. The nanoparticles were found to induce mitochondrial-mediated apoptosis driven by the apoptotic genes such as BAX and Bcl₂. Molybdenum being a cofactor for the majority of metabolic enzymes could have triggered the selective internalization of the nanoparticles which in turn could have modified the granularity of the cytoplasm and subsequently lead to mitochondrial-mediated apoptosis. Further, the anti-angiogenic property of MoO₃ nanoparticles was corroborated using Chick chorioallantoic membrane (CAM) assay and aortic ring assay. Taken together , unraveling the role of MoO₃ nanoparticles in cancer and angiogenesis opens up venues for nano biological intervention of selective cancer cell targeting with minimal damage to the normal cells using natural trace elements that are generally known to influence various metabolic enzymes.

J. Indrakumar, and P. S. Korrapati,Steering Efficacy of Nano Molybdenum Towards Cancer: Mechanism of Action, Biol Trace Elem Res, 2019.

Molybdenum oxide nanoparticles therapy breast cancer

33 Plasmonic MoO3^-x nanoparticles incorporated in Prussian blue frameworks exhibit highly efficient dual photothermal/photodynamic therapy

Development of near infrared (NIR) light-responsive nanomaterials for high performance multimodal phototherapy within a single nanoplatform is still challenging in technology and biomedicine. Herein, a new phototherapeutic nanoagent based on FDA-approved Prussian blue (PB) functionalized oxygen-deficient molybdenum oxide nanoparticles (MoO₃^-x NPs) is strategically designed and synthesized by a facile one-pot size/morphology-controlled process. The as-prepared PB-MoO₃^-x nanocomposites (NCs) with a uniform particle size of similar to 90 nm and high water dispersibility exhibited strong optical absorption in the first biological window, which is induced by plasmon resonance in an oxygen-deficient MoO₃^-x semiconductor. More importantly, PB-MoO₃^-x NCs not only exhibited a high photothermal conversion efficiency of similar to 63.7% and photostability but also offered a further approach for the generation of reactive oxygen species (ROS) upon singular NIR light irradiation which significantly improved the therapeutic efficiency of the PB agent. Furthermore, PB-MoO₃^-x NCs showed a negligible cytotoxic effect in the dark, but an excellent therapeutic effect toward two triple-negative breast cancer (TNBC) cell lines at a low concentration (20 mu g mL(^-1)) of NCs and a moderate NIR laser power density. Additionally, efficient tumor ablation and metastasis inhibition in a 4T₁ TNBC mouse tumor model can also be realized by synergistic photothermal/photodynamic therapy (PTT/PDT) under a single continuous NIR wave laser. Taken together, this study paved the way for the use of a single nanosystem for multifunctional therapy.

A. H. Odda, Y. C. Xu, J. Lin, G. Wang, N. Ullah, A. Zeb, K. Liang, L. P. Wen, and A. W. Xu,Plasmonic MoO3-x nanoparticles incorporated in Prussian blue frameworks exhibit highly efficient dual photothermal/photodynamic therapy, Journal of Materials Chemistry B, 2019, 7, 2032-2042.

ANTITUMOUR

Molybdenum(II) complexes with p-substituted BIAN ligands: synthesis, characterization, biological activity and computational study

New complexes [Mo(eta3-C3H5)X(CO)2(4-Y-BIAN)] (4-Y-BIAN = bis(4-Y-phenyl)-acenaphthenequinonediimine), with X = Br and Y = H, Me, OMe, COOH and X = Cl, Y = OMe, as well as the cation with X = NCMe and Y = OMe were synthesized, expanding the scope of this family. Two single crystal X-ray structures (X = Br, Y = Me, OMe) display a less symmetric arrangement (axial isomer), where one N donor atom is trans to the allyl group and the second to one CO. DFT studies showed similar energies for the two possible isomers of the complexes, with a very small preference for the observed axial isomer. The HOMO of the complexes is localized in the metal and the HOMO-1 of the oxidized species has a contribution from the BIAN ligand, while the LUMO is fully localized in BIAN. Electrochemical studies showed one process corresponding to the oxidation of Mo(ii) to Mo(iii) for complexes with X = Br, Y = H, Me, and two oxidation reactions for those with X = Br, Y = Cl, OMe, while the COOH derivative exhibited no oxidation wave. The antitumor effect of the complexes with X = Br was tested in cancer lines, and the H and OMe complexes were particularly active, with EC50 values below 8 muM in HeLa cell lines. The DNA binding constants determined by titration experiments were comparable with those of doxorubicin and ethidium bromide, suggesting a mechanism of action based on intercalation in DNA.

S. Quintal, M. J. Pires da Silva, S. R. M. Martins, R. Sales, V. Felix, M. G. B. Drew, M. Meireles, A. C. Mourato, C. D. Nunes, M. S. Saraiva, M. Machuqueiro, and M. J. Calhorda,Molybdenum(ii) complexes with p-substituted BIAN ligands: synthesis, characterization, biological activity and computational study, Dalton transactions (Cambridge, England : 2003), 2019.

Therapeutic Uses of Molybdenum

Molybdenum is an essential trace element and is a component of vitamin and mineral supplements. Some therapeutic uses of molybdenum compounds are described in this section.

THERAPEUTIC

Mo NANOCLUSTERS

Synthesis of fluorescent molybdenum nanoclusters at ambient temperature and their application in biological imaging

We introduce for first time a facile protocol for the rapid synthesis of a molybdenum nanoclusters (MoNCs) at room temperature using thiolated dithiothreitol (DTT) as capping agents. The initial fluorescence from the MoNCs is observed in 30min and further intensified in 48h. The mean diameter of nanoclusters was found to be 1.5nm with -77mV zeta potential. The nanoclusters have good stability in all tested pH ranges, especially between pH7 and 10. This property makes the nanomaterial to be ideal for many types of possible biological/biomedicine applications such as drug delivery or biological imaging. The quantum yield of thiolated MoNCs was calculated to be 59% which is higher than the noble metal nanoclusters reported earlier. The mechanism of formation of MoNCs was investigated using the UV-Vis spectroscopy and cyclic voltammetry. Owing to these characteristics, MoNCs were used for imaging of HaCaT and A549 cancer cells. The current approach on novel synthesis of MoNCs is found to be a superior alternative to conventional/popular MoS2 based on the method of synthesis, particle size, and fluorescence quantum yield. The current approach on the MoNCs has created a new platform for future biomedicine applications.

A. K. Sharma, S. Pandey, N. Sharma, and H. F. Wu,Synthesis of fluorescent molybdenum nanoclusters at ambient temperature and their application in biological imaging, Materials science & engineering. C, Materials for biological applications, 2019, 99, 1-11.

THERAPEUTIC

MoS₂ BIOSENSOR CANCER

Highly efficient Polyaniline-MoS₂ hybrid nanostructures based biosensor for cancer biomarker detection

In this work, polyaniline nanospindles have been synthesized using iron oxide as sacrificial template. These nanospindles were utilized for the fabrication of PANI-MoS₂ nanoflower architectures via hydrothermal route. The electrostatic interaction between PANI and MoS₂ improves the conductivity and provides more direct paths for charge transportation. SEM, TEM, XRD, Raman Spectroscopy techniques were employed to explore the crystal structure, and morphological properties of the PANI-MoS₂ nanocomposite. Furthermore, an electrochemical biosensing platform based on PANI-MoS₂ nanocomposite was fabricated for the specific detection of chronic myelogenous leukemia (CML) by using electrochemical impedance spectroscopy technique. The binding interactions between the pDNA/PANI-MoS₂/ITO bioelectrode and target DNA sequence were also studied. The biosensor exhibits high sensitivity and wide detection range (10(-6) M to 10(-17) M) of target DNA with low detection limit (3x₁₀(^-18) M). Additionally, the specificity studies of the genosensor with various target DNA sequences (complementary, noncomplementary and one base mismatch) and real samples analysis of CML shows its potential for clinical diagnostics.

A. Soni, C. M. Pandey, M. K. Pandey, and G. Sumana,Highly efficient Polyaniline-MoS₂ hybrid nanostructures based biosensor for cancer biomarker detection, Analytica chimica acta, 2019, 1055, 26-35.

MoS₂ CANCER

Dual-responsive molybdenum disulfide/copper sulfide-based delivery systems for enhanced chemo-photothermal therapy

Molybdenum disulfide (MoS₂)-based drug delivery systems have shown considerable potential in cancer nanomedicines. In this work, a multifunctional nanoplatform comprising MoS₂ nanosheets decorated with copper sulfide (CuS) and further functionalized with polyethylene glycol (PEG) is reported. The resultant material has a particle size of approximately 115nm, and can be loaded with doxorubicin (DOX) to a loading capacity of 162.3mg DOX per g of carrier. Drug release is triggered by two stimuli (near infrared (NIR) irradiation and pH), and the carrier is shown to have excellent colloidal stability. The presence of both MoS₂ and CuS leads to very high photothermal conversion efficiency (higher than with MoS₂ alone). In vitro experiments revealed that the blank CuS-MoS₂-SH-PEG carrier is biocompatible, but that the synergistic application of chemo-photothermal therapy (in the form of CuS-MoS₂-SH-PEG loaded with DOX and NIR irradiation) led to greater cell death than either chemotherapy (CuS-MoS₂-SH-PEG (DOX) but no NIR) or photothermal therapy (CuS-MoS₂-SH-PEG with NIR). A cellular uptake study demonstrated that the nanoplatform can efficiently enter tumor cells, and that uptake is enhanced when NIR is applied. Overall, the functionalized MoS₂ material developed in this work exhibits great potential as an efficient system for dual responsive drug delivery and synergistic chemo-photothermal therapy. The route employed in our work thus provides a strategy to enhance photothermal efficacy for transition metal dichalcogenide drug delivery systems.

X. Zhang, J. Wu, G. R. Williams, Y. Yang, S. Niu, Q. Qian, and L. M. Zhu,Dual-responsive molybdenum disulfide/copper sulfide-based delivery systems for enhanced chemo-photothermal therapy, Journal of colloid and interface science, 2019, 539, 433-441.

THERAPEUTIC

Tumor-Targeted and Biocompatible MoSe₂ Nanodots@Albumin Nanospheres as a Dual^- Modality Therapy Agent for Synergistic Photothermal Radiotherapy

Integrating multiple tumor therapy functions into one nanoplatform has been a new tumor therapy strategy in recent years. Herein, a dual-modality therapy agent consisting of molybdenum selenide nanodots ( MoSe₂ NDs) and bovine serum albumin (BSA) assembled nanospheres ( MoSe₂@BSA NSs) was successfully synthesized. After conjugation of folic acid (FA) molecules via polyethylene glycol (PEG) "bridges," the FA^- MoSe₂@BSA NSs were equipped with tumor-targeting function. The BSA and PEG modifications provided the unstable MoSe₂ NDs with excellent physiological stability. Since the end-product FA^- MoSe₂@BSA NSs had strong near-infrared (NIR) and X-ray absorbance properties, they exhibited good photothermal properties with excellent photothermal stability and radio-sensitization ability, hence, were explored as photothermal radiotherapy agents. In vitro and in vivo experiments indicated that the FA^- MoSe₂@BSA NSs possessed highly efficient tumor-targeting effect, great biocompability, and synergistic photothermal radiotherapy effect. This work suggests that such biocompatible FA^- MoSe₂@BSA NSs may be a promising multifunctional dual-modality tumor therapy agent for use in combination tumor therapy.

F. Qi, and R. Liu,Tumor-Targeted and Biocompatible MoSe₂ Nanodots@Albumin Nanospheres as a Dual^- Modality Therapy Agent for Synergistic Photothermal Radiotherapy, Nanoscale research letters, 2019, 14, 67.

infrared light energy. https://www.sciencedirect.com/topics/engineering/photothermal-therapy.]

Molybdenum cofactor deficiency type B knock-in mouse models carrying patient-identical mutations and their rescue by singular AAV injections

Molybdenum cofactor deficiency is an autosomal, recessively inherited metabolic disorder, which, in the absence of an effective therapy, leads to early childhood death due to neurological deterioration. In type A of the disease, cyclic pyranopterin monophosphate (cPMP) is missing, the first intermediate in the biosynthesis of the cofactor, and a biochemical substitution therapy using cPMP has been developed. A comparable approach for type B of the disease with a defect in the second step of the synthesis, formation of molybopterin, so far has been hampered by the extreme instability of the corresponding metabolites. To explore avenues for a successful and safe gene therapy, knock-in mouse models were created carrying the mutations c.88C>T (p.Q30X) and c.726_727delAA, which are also found in human patients. Recombinant adeno-associated viruses (rAAVs) were constructed and used for postnatal intrahepatic injections of MoCo-deficient mice in a proof-of-concept approach. Singular administration of an appropriate virus dose in 60 animals prevented the otherwise devastating phenotype to a variable extent. While untreated mice did not survive for more than 2 weeks, some of the treated mice grew up to adulthood in both sexes.

J. Reiss, molybdenum cofactor deficiency type B knock-in mouse models carrying patient-identical mutations and their rescue by singular AAV injections, Human genetics, 2019.

Cysteamine functionalized MoS₂ quantum dots inhibit amyloid aggregation

In this study, cysteamine-functionalized molybdenum disulfide quantum dots ( MoS₂ QDs) were synthesized by a one-pot hydrothermal method. A range of techniques including of Thioflavin T and 8-Anilino^-1-naphthalenesulfonic acid fluorescence assays, circular dichroism, and transmission electron microscope have been employed to determination the efficacy of MoS₂ QDs on the inhibition/reversion of fibrillation and hindering cytotoxicity induced by protofibrils and amyloid fibrils of bovine serum albumin (BSA). Results demonstrated that MoS₂ QDs could effectively inhibit the fibrillogenesis and destabilize preformed fibrils of BSA in a concentration-dependent manner. Cytotoxicity protection and imagine on Hela cells was investigated using the methyl thiazolyl tetrazolium (MTT) assay. It was found that MoS₂ QDs not only has good biocompatibility, low toxicity and good cell penetration, but also could effectively decrease the cytotoxicity caused by the formed fibrils of BSA. The results obtained in this work suggested the potential biological application of MoS₂ QDs in therapeutics and provided new insight into the design of multifunctional nanomaterials for amyloid-related diseases.

L. J. Sun, L. Qu, R. Yang, L. Yin, and H. J. Zeng,Cysteamine functionalized MoS₂ quantum dots inhibit amyloid aggregation, International journal of biological macromolecules, 2019, 128, 870-876.

Highly efficient Polyaniline- MoS₂ hybrid nanostructures based biosensor for cancer biomarker detection

In this work, polyaniline nanospindles have been synthesized using iron oxide as sacrificial template. These nanospindles were utilized for the fabrication of PANI^- MoS₂ nanoflower architectures via hydrothermal route. The electrostatic interaction between PANI and MoS₂ improves the conductivity and provides more direct paths for charge transportation. SEM, TEM, XRD, Raman Spectroscopy techniques were employed to explore the crystal structure, and morphological properties of the PANI^- MoS₂ nanocomposite. Furthermore, an electrochemical biosensing platform based on PANI^- MoS₂ nanocomposite was fabricated for the specific detection of chronic myelogenous leukemia (CML) by using electrochemical impedance spectroscopy technique. The binding interactions between the pDNA/PANI^- MoS₂/ITO bioelectrode and target DNA sequence were also studied. The biosensor exhibits high sensitivity and wide detection range (10(-6) M to 10(-17) M) of target DNA with low detection limit (3-10(-18) M). Additionally, the specificity studies of the genosensor with various target DNA sequences (complementary, noncomplementary and one base mismatch) and real samples analysis of CML shows its potential for clinical diagnostics. (C) 2018 Elsevier B.V. All rights reserved.

A. Soni, C. M. Pandey, M. K. Pandey, and G. Sumana,Highly efficient Polyaniline^- MoS₂ hybrid nanostructures based biosensor for cancer biomarker detection, Analytica Chimica Acta, 2019, 1055, 26-35.

Association between selected essential trace element concentrations in umbilical cord and risk for cleft lip with or without cleft palate: A case-control study

A deficiency or excess of zinc (Zn), selenium (Se), cobalt (Co), molybdenum (Mo), or manganese (Mn) may interfere with fetal organogenesis. However, the impact of these essential trace elements on the occurrence of cleft lip with or without cleft palate (CL+/-P) remains to be elucidated. We aimed to investigate the associations between the amounts of Zn, Se, Co, Mo, and Mn in umbilical cord tissue and risk for CL+/-P. This case-control study included 200 controls without congenital malformations and 88 CL+/-P cases. Zn, Se, Co, Mo, and Mn concentrations in the umbilical cord were determined using inductively coupled plasma mass spectrometry. Information was collected on demographics, lifestyle behaviors, and dietary intake. The median concentrations of Zn in cases of CL+/-P and cleft lip with cleft palate (CLP), of Se in cases of CL+/-P and cleft lip only (CLO), and of Co in cases of CLO were lower than in the controls. In utero exposure to higher levels of Zn was associated with reduced risk for CL+/-P (OR=0.44, 95% CI, 0.20-0.93) and for CLP (OR=0.35, 95% CI, 0.14-0.86), and a higher level of Se was associated with reduced risk for CL+/-P and CLO, with ORs of 0.47 (95% CI, 0.23-0.95) and 0.22 (95% CI, 0.08-0.67), respectively. By contrast, higher levels of Mo in the umbilical cord were associated with 2.52-fold (95% CI, 1.23-5.20) and 2.59-fold (95% CI, 1.12-5.95) higher risk for CL+/-P and CLP, respectively. No association was found between Co or Mn and risk for CL+/-P. In conclusion, in utero exposure to higher levels of Zn and Se was associated with reduced risk for CL+/-P, but higher levels of Mo were associated with increased risk for CL+/-P.

W. Ni, W. Yang, J. Yu, Z. Li, L. Jin, J. Liu, Y. Zhang, L. Wang, and A. Ren,Association between selected essential trace element concentrations in umbilical cord and risk for cleft lip with or without cleft palate: A case-control study, The Science of the total environment, 2019, 661, 196-202.

HUMAN HEALTH

Trace element profiles in pregnant women's sera and umbilical cord sera and influencing factors: Repeated measurements

In utero exposure to toxic heavy metals and deficient or excessive essential trace elements during pregnancy may have adverse effects on pregnant women and their offsprings, which are of great concern. The objective of the present study was to characterize serum concentrations of multiple trace elements at multiple time points during pregnancy in Chinese women. Three thousand four hundred and sixteen pregnant women in total were included from MABC (Ma'anshan Birth Cohort) study. Fasting sera in the morning and questionnaires were obtained at three separate follow-up visits. Nineteen trace elements from serum samples were analyzed, including aluminum (Al), vanadium (V), chromium (Cr), manganese (Mn), iron (Fe), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), selenium (Se), cadmium (Cd), barium (Ba), thallium (Tl), lead (Pb), calcium (Ca), magnesium (Mg), mercury (Hg) and molybdenum (Mo). The total detection rates for most elements were 100% rather than Ni (99.98%), As (99.97%), Cd (99.6%), Ba (99.9%), Pb (99.8%), Hg (99.8%). The concentration distributions of 19 elements varied vastly. Median concentrations for all trace elements ranged from 38.5 ng/L to 102.9 mg/L. The moderate interclass correlation coefficients (ICCs) were observed for Co, Cu, Se and Hg, ranging from 0.40 to 0.62; the lower ICCs, ranging from 0.13 to 0.32 were for Fe, Zn, Cd, Ba, Tl, Mg and Mo. The intraclass correlation effects were not observed for the remaining elements, such as Al, V, Cr, Mn, Ni, As and Pb. The concentrations of each element between three time points were significantly different; significant differences were also found between any two time points except for Ni, Cd and Mo. Many factors could affect the levels of trace elements, and a very important factor of them was season. Consequently, a single measurement of elements in sera seems not enough to describe exposure levels throughout pregnancy; additionally, season affected exposure levels of trace elements with moderate ICCs showed certain regularity. Future analyses should take sampling seasons into consideration carefully.

C. M. Liang, X. Y. Wu, K. Huang, S. Q. Yan, Z. J. Li, X. Xia, W. J. Pan, J. Sheng, Y. R. Tao, H. Y. Xiang, J. H. Hao, Q. N. Wang, F. B. Tao, and S. L. Tong,Trace element profiles in pregnant women's sera and umbilical cord sera and influencing factors: Repeated measurements, Chemosphere, 2019, 218, 869-878.

THERAPEUTIC

Cationic octahedral molybdenum cluster complexes functionalized with mitochondria-targeting ligands: photodynamic anticancer and antibacterial activities

Octahedral molybdenum cluster complexes have recently come forth as pertinent singlet oxygen photosensitizers towards biological applications. Still, their phototoxic efficiency in the absence of nanocarriers remains limited due to their poor cellular uptake. Here, two cationic octahedral molybdenum cluster complexes, bearing carboxylate ligands with triphenylphosphonium (1) or N-methyl pyridinium (2) mitochondria-targeting terminal functions, have been designed and synthesized. Their photophysical properties in water and in vitro biological activity were investigated in the context of blue-light photodynamic therapy of cancer and photoinactivation of bacteria. Upon blue light irradiation, complex 1 displays red luminescence with a quantum yield of 0.24 in water, whereas complex 2 is much less emissive (PhiL < 0.01). Nevertheless, both complexes efficiently produce singlet oxygen, O2(1Deltag). Complex 1 is rapidly internalized into HeLa cells and accumulated in mitochondria, followed by relocation to lysosomes and clearance at longer times. In contrast, the more hydrophilic 2 is not internalized into HeLa cells, highlighting the effect of the apical ligands on the uptake properties. The treatment with 1 results in an intensive phototoxic effect under 460 nm irradiation (IC50 = 0.10 +/- 0.02 muM), which exceeds by far those previously reported for octahedral cluster-based molecular photosensitizers. The ratio between phototoxicity and dark toxicity is approximately 50 and evidences a therapeutic window for the application of 1 in blue-light photodynamic therapy. Complex 1 also enters and efficiently photoinactivates Gram-positive bacteria Enterococcus faecalis and Staphylococcus aureus, documenting its suitability as a blue-light photosensitizer for antimicrobial applications.

K. Kirakci, J. Zelenka, M. Rumlova, J. Cvacka, T. Ruml, and K. Lang,Cationic octahedral molybdenum cluster complexes functionalized with mitochondria-targeting ligands: photodynamic anticancer and antibacterial activities, Biomaterials science, 2019.

THERAPEUTIC USES OF MOLYBDENUM

Antibacterial MoO₃

Bactericidal efficacy of molybdenum oxide nanoparticles against antimicrobial-resistant pathogens

Multidrug-resistant bacteria pose a major threat to effective antibiotics and alternatives to fight multidrug-resistant pathogens are needed. We synthetized molybdenum oxide (MoO3) nanoparticles (NP) and determined their antibacterial activity against 39 isolates: (i) eight Staphylococcus aureus, including representatives of methicillin-resistant S. aureus epidemic clones; (ii) six enterococci, including vancomycin-resistant isolates; and (iii) 25 Gram-negative isolates (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, Enterobacter cloacae), including extended spectrum beta-lactamases and carbapenemases producers. All isolates showed a MoO3 NP MIC of 700-800 mg l(-1). MoO3 NP produced a clear inhibition zone for S. aureus and all Gram-negative isolates at concentrations >/=25 mg ml(-1) and >/=50 mg ml(-1) for enterococci. When the NP solutions were adjusted to pH ~7, the biocidal activity was completely abolished. MoO3 NP create an acidic pH and show a universal antimicrobial activity against susceptible and resistant isolates belonging to the most relevant bacterial species responsible for hospital-acquired infections.

E. Lopes, S. Picarra, P. L. Almeida, H. de Lencastre, and M. Aires-de-Sousa,Bactericidal efficacy of molybdenum oxide nanoparticles against antimicrobial-resistant pathogens, Journal of medical microbiology, 2018.

Skin Cancer MoO₃

Selectivity and sensitivity of molybdenum oxide-polycaprolactone nanofiber composites on skin cancer: Preliminary in-vitro and in-vivo implications

Cancer nanomedicine has emerged as a revolution in the last decade opening up promising strides for the cancer treatment. The major challenge in these therapeutic approaches resides in the failure of clinical trials owing to the immunological cancer microenvironment. Therefore, the success of next generation nanomedicine depends on tunable physicochemical nanomaterial design and corresponding clinical trials by integrating targeted delivery with mitigated toxicity. The present study deals with the fabrication of nanofibrous scaffold impregnated with molybdenum nanoparticles for targeted skin cancer therapeutics. Molybdenum oxide, a transitional metal oxide is gaining rapid importance due to its vital role in cellular and molecular metabolism. Polycaprolactone nanofibers were chosen as a matrix to localize the nanoparticles topically facilitating selective apoptosis of the tumor cells over the normal cells with mitigated side effects. The scaffold was designed to tailor the physicochemical, mechanical and biological suitability for skin cancer (melanoma and non melanoma). The designed scaffold was found to reduce more than 50% cell viability of the cancer cells selectively through apoptosis as confirmed using AO/PI staining and the probable mechanism could be attributed to the induction of mitochondria dependent apoptosis as observed by JC1 dye staining. In-vivo trials in zebra fish were found to reduce cancer progression by more than 30% in 14 days. The fabricated molybdenum trioxide nano constructs not only serve as tunable targeted systems but also open venues capable of ferrying chemotherapeutic drugs sparing normal cells alleviating the trauma due to side effects.

Janani, R. Lakra, M. S. Kiran, and P. S. Korrapati,Selectivity and sensitivity of molybdenum oxide-polycaprolactone nanofiber composites on skin cancer: Preliminary in-vitro and in-vivo implications, Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS), 2018, 49, 60-71

Liver Cancer

Crystal Structure and Biological Evaluation of Two Novel Organic-Inorganic Hybrid Materials as Antitumor Agents in the Treatment of Liver Cancer

Two novel organic-inorganic hybrid materials {(Hbiz)(6)[(As₂AsMo₁₈O₆₂)-As-III-Mo-V-O-VI]}center dot H₂O (1, biz = benzimidazole) and (dim) [AS(2)(III)As(V)Mo(18)(VI)O(62)] [2, dim = 1,6-bis(imidazol)hexane] have been successfully obtained by using the molybdenum arsenate and different N donor organic compounds and determined through X-ray single-crystal diffraction technique. The in vitro cytotoxicity of compounds 1 and 2 was then investigated against three human liver tumor cell lines (SMMC₇₇₂₁, Bel^-7402, and MHCC₉₇) by MIT assay. It was found that the two compounds showed potent use as antitumor agents against the aforementioned cell lines.

B. H. Song, C. Li, and G. F. An,Crystal Structure and Biological Evaluation of Two Novel Organic-Inorganic Hybrid Materials as Antitumor Agents in the Treatment of Liver Cancer, Journal of Chemistry, 2018.

Facile preparation of molybdenum (VI) oxide - Modified graphene oxide nanocomposite for specific enrichment of phosphopeptides

To promote the development of phosphoproteome analysis in highly selective efficient tracing phosphorylated proteins or peptides, views of researches should not confined with intrinsic materials and their modification. New materials are supposed to be explored for phosphoproteome analysis. In this work, we first introduced Molybdenum (VI) oxide (MoO₃) into phosphoproteome, loading on the graphene oxide (GO) nanosheets forming MoO₃/GO nanocomposites by a simple two-step strategy. The GO nanosheets offered MoO₃ a perfect stable platform for separation and concentration and MoO₃ exhibited wonderful property in enriching phosphopeptides with highly selectivity and sensitivity on GO nanosheets. Specifically, the as-synthesized MoO₃/GO nanocomposites exhibited excellent specificity (beta-casein: BSA = 1:1000), high detection sensitivity (1 fmol/mL) and well recovery (91.13%) in enriching phosphopeptides by metal oxide affinity chromatography (MOAC). Moreover, the as-synthesized MoO₃/GO nanocomposites provided effective enrichment of phosphopeptides from nonfat milk (a total of twelve phosphopeptides signals) and human serum (a total of four endogenous phosphopeptides signals), displaying great biological compatibility, which demonstrated that the MoO₃/GO nanocomposites is a promising candidate in selectively identifying and determining low-abundance phosphorylated peptides in biological sample. (C) 2017 Elsevier B.V. All rights reserved.

Sun, H. F_., Zhang, Q. Q_., Zhang, L_., Zhang, W. B_., and Zhang, L. Y_.,Facile preparation of molybdenum (VI) oxide - Modified graphene oxide nanocomposite for specific enrichment of phosphopeptides, Journal of Chromatography A, 2017, 1521, 36-43

Effects of two-dimensional materials on human mesenchymal stem cell behaviors

Graphene, a typical two-dimensional (2D) material, is known to affect a variety of stem cell behaviors including adhesion, spreading, growth, and differentiation. Here, we report for the first time the effects of four different emerging 2D materials on human adipose-derived mesenchymal stem cells (hADMSCs). Graphene oxide (GO), molybdenum sulfide (MoS₂), tungsten sulfide (WS₂), and boron nitride (BN) were selected as model two-dimensional materials and were coated on cell-culture substrates by a drop-casting method. Acute toxicity was not observed with any of the four different 2D materials at a low concentration range (<5 mug/ml). Interestingly, the 2D material-modified substrates exhibited a higher cell adhesion, spreading, and proliferation when compared with a non-treated (NT) substrate. Remarkably, in the case of differentiation, the MoS₂-, WS₂-, and BN-modified substrates exhibited a better performance in terms of guiding the adipogenesis of hADMSCs when compared with both NT and GO-modified substrates, based on the mRNA expression level (qPCR) and amount of lipid droplets (ORO staining). In contrast, the osteogenesis was found to be most efficiently induced by the GO-coated substrate (50 mug/mL) among all 2D-material coated substrates. In summary,.

Suhito, I. R_., Han, Y_., Kim, D. S_., Son, H_., and Kim, T. H_.,Effects of two-dimensional materials on human mesenchymal stem cell behaviors, Biochemical and biophysical research communications, 2017, 493, 578-584.

Label-free and recalibrated multilayer MoS₂ biosensor for point-of-care diagnostics

Molybdenum disulfide (MoS₂) field-effect transistor (FET)-based biosensors have attracted a significant attention as promising candidates for highly sensitive, label-free biomolecule detection devices. In this paper, toward practical applications of biosensors, we demonstrate reliable and quantitative detection of a prostate cancer biomarker using the MoS₂-FET biosensor in a non-aqueous environment by reducing non-specific molecular binding events and realizing uniform chemisorption of anti-PSA onto the MoS₂ surface. A systematic and statistical study on the capability of the proposed device is presented, and the biological binding events are directly confirmed and characterized through intensive structural and electrical analysis. Our proposed biosensor can reliably detect various PSA concentrations with a limit of 100 fg/mL. Moreover, rigorous theoretical simulations provide a comprehensive understanding of the operating mechanism of the MoS₂-FET biosensors, and further suggests the enhancement of the sensitivity through engineering device design parameters.

Park, H_., Han, G. C_., Lee, S. W_., Lee, H_., Jeong, S. H_., Naqi, M_., AlMutairi, A_., Kim, Y. J_., Lee, J_., Kim, W. J_., Kim, S_., Yoon, Y_., and Yoo, G_.,Label-free and recalibrated multilayer MoS₂ biosensor for point-of-care diagnostics, ACS Appl Mater Interfaces, 2017.

Enhancing the colloidal stability and surface functionality of molybdenum disulfide (MoS₂) nanosheets with hyperbranched polyglycerol for photothermal therapy

Molybdenum disulfide (MoS₂) nanosheets are gaining increasing attention due to their attractive properties and myriads of potential applications. However, challenges in the enhancement of their colloidal stability and surface functionality still remain and significantly restrict their practical applications. Herein, we present a viable approach to functionalize MoS₂ nanosheets with multihydroxy hyperbranched polyglycerol (HPG) shell by surface-initiated ring-opening polymerization technique. The grafting of HPG from the surface of MoS₂ nanosheet yielded MoS₂-g-HPG nanohybrid with excellent water dispersibility, good biocompatibility, and greatly enhanced colloidal stability against pH change, ionic strength variation and long-term storage. The MoS₂-g-HPG also exhibited excellent light-to-heat conversion capability for in vitro photothermal therapy application. Meanwhile, the MoS₂-g-HPG showed favorable surface functionality owing to its numerous surface hydroxyl groups, as demonstrated by the conjugation of functional molecules such as fluorescent dye rhodamine B. As such, this paper opens up new opportunities to empower MoS₂ nanosheets and other two-dimensional inorganic nanosheets with desired properties for various applications.

Huang, B., Wang, D., Wang, G., Zhang, F., and Zhou, L.,Enhancing the colloidal stability and surface functionality of molybdenum disulfide (MoS2) nanosheets with hyperbranched polyglycerol for photothermal therapy, Journal of colloid and interface science, 2017, 508, 214-221.

Modified cyclopentadienyl molybdenum compounds with enhanced cytotoxic activity towards MOLT-4 leukaemia cells

A series of new cyclopentadienyl molybdenum compounds bearing substituted phenanthroline ligands [(eta(5)-C₅H₄CH₂C₆H₄X^-4)Mo(CO)₂(L-N,L-N)][BF₄] (X = F, Cl, Br; L-N,L-N=phen, 5-NH^₂-phen, 4,7-Ph^-2-phen) was prepared and characterized using infrared and NMR spectroscopies. Crystal structures of [(eta(5)-C₅H₄CH₂C₆H₄F^-4)Mo(CO)(2)(NCMe)(2)][BF₄], [(eta(5)-C₅H₄CH₂C₆H₄X^-4)Mo(CO)(2)(phen)][BF₄] (X = F, Cl, Br) and [(eta(5)-C₅H₄CH₂C₆H₄Cl^-4)Mo(CO)(2)(4,7^-Ph-2-phen)][BF₄](4,7^-Ph-2-phen)HBF₄ were determined using X-ray diffraction analysis. Biological studies revealed a strong cytotoxic effect of the chelating ligands. Although the cytostatic effect of the halogen in the side chain of the cyclopentadienyl ring is negligible, it could be used for future post-modification of these types of cytotoxic active molybdenum-based compounds.

Honzickova, I_., Vinklarek, J_., Ruzickova, Z_., Rezacova, M_., and Honzicek, J_.,Modified cyclopentadienyl molybdenum compounds with enhanced cytotoxic activity towards MOLT-4 leukaemia cells, Applied Organometallic Chemistry, 2017, 31.

MoS₂-based sensor for the detection of miRNA in serum samples related to breast cancer

Early diagnosis of cancer is critical for the treatment of patients, and can reduce the risk of death. Breast cancer is one of the most common malignant tumors in women, and miR-21, as an important breast cancer biomarker, can be helpful for the early diagnosis of breast cancer. In this work, we have developed an efficient, sensitive and specific fluorescence sensor based on the novel nanomaterial molybdenum disulfide (MoS₂) to detect miR-21. The novel nanomaterial MoS₂ was introduced to a fluorescent dye-labeled DNA probe to fabricate the fluorescence sensor, and then non-complementary miRNA, one-base mismatched miRNA and complementary miR-21 were separately introduced to the sensor to hybridize with the DNA probe. By monitoring the change of the fluorescence signal before and after DNA-miRNA hybridization, miR-21 could be detected. We found that the sensor could discriminate complementary miR-21 from one-base mismatched miRNA and non-complementary miRNA successfully. Furthermore, the biosensor was able to detect miR-21 down to a concentration of 500 pM, and the detection could be completed in only 40 min. The novel MoS₂ fluorescence sensor, with the advantages of fast analysis, high sensitivity and specificity, and low cost, is suitable for miR-21 detection which is of great importance for the early diagnosis of breast cancer. What's more, the novel sensor, with high sensitivity and selectivity, was also used to detect miR-21 in serum samples, making it a promising method for detection in real samples from patients with cancer. Thus the novel MoS₂ fluorescence sensor shows huge potential for early diagnosis of cancer.

B. J. Cai, S. Guo, and Y. Li,MoS₂-based sensor for the detection of miRNA in serum samples related to breast cancer, Analytical Methods, 2018, 10, 230-236.

Corrosion and surface modification on biocompatible metals: A review

Corrosion prevention in biomaterials has become crucial particularly to overcome inflammation and allergic reactions caused by the biomaterials' implants towards the human body. When these metal implants contacted with fluidic environments such as bloodstream and tissue of the body, most of them became mutually highly antagonistic and subsequently promotes corrosion. Biocompatible implants are typically made up of metallic, ceramic, composite and polymers. The present paper specifically focuses on biocompatible metals which favorably used as implants such as 316L stainless steel, cobalt-chromium-molybdenum, pure titanium and titanium -based alloys. This article also takes a close look at the effect of corrosion towards the implant and human body and the mechanism to improve it. Due to this corrosion delinquent, several surface modification techniques have been used to improve the corrosion behavior of biocompatible metals such as deposition of the coating, development of passivation oxide layer and ion beam surface modification. Apart from that, surface texturing methods such as plasma spraying, chemical etching, blasting, electropolishing, and laser treatment which used to improve corrosion behavior are also discussed in detail. Introduction of surface modifications to biocompatible metals is considered as a "best solution" so far to enhanced corrosion resistance performance; besides achieving superior biocompatibility and promoting osseointegration of biocompatible metals and alloys. (C) 2017 Elsevier B.V. All rights reserved.

R. I. M. Asri, W. S. W. Harun, M. Samykano, N. A. C. Lah, S. A. C. Ghani, F. Tarlochan, and M. R. Raza,Corrosion and surface modification on biocompatible metals: A review, Materials Science & Engineering C-Materials for Biological Applications, 2017, 77, 1261-1274.

Neutron-activatable needles for radionuclide therapy of solid tumors

Various approaches have been undertaken to enhance the delivery of therapeutic agents, including tissue-killing radionuclides, into solid tumors. Here, we describe the preparation of conical needles composed of Ti and Mo coated by pulsed laser deposition or chemical vapor deposition with elements (Ho and Re) that can readily yield radioactive isotopes following irradiation in a neutron flux. The radioactive needles, whose design were based on solid microneedle arrays used in transdermal drug delivery, can be produced with minimal handling of radioactivity and subsequently inserted into tumors as a means of internal radiation therapy. Ho and Re were specifically chosen because of their large neutron capture cross-sections as well as the desirable radiotherapeutic properties of the resultant radionuclides. Neutron-absorbing shields were also developed to prevent the production of unwanted radionuclides after neutron irradiation of the needle base materials. Neutron activation calculations showed that therapeutically significant amounts of radionuclides can be produced for treating solid tumors. Stability studies demonstrated that Re did not leach off the Mo needles. These coated neutron-activatable needles offer a new approach to internal radiation therapy of tumors that allows precise tailoring of the absorbed radiation dose delivered to the tumor by controlling the coating thickness and the irradiation time. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3273-3280, 2017.

J. Kim, R. J. Narayan, X. Lu, and M. Jay,Neutron-activatable needles for radionuclide therapy of solid tumors, Journal of biomedical materials research. Part A, 2017, 105, 3273-3280.

MoS₂ nanosheets encapsulated in sodium alginate microcapsules as microwave embolization agents for large orthotopic transplantation tumor therapy

In recent years, it is prevalent to treat various kinds of the tumors through microwave ablation method. However, it is still very difficult to ablate large tumors by the traditional microwave ablation therapy. In this work, an effective microwave embolization agent designed by encapsulating molybdenum sulfide nanosheets in the sodium alginate microcapsules, denoted as MSMCs, was prepared for the effective therapy of large tumor. The toxicity evaluation showed that MSMC had a good biocompatibility in vitro. The in vitro and in vivo experiments demonstrated that the MSMC was an excellent embolic and microwave susceptible agent that could be used for dual-enhanced microwave ablation therapy. As such, the MSMC showed excellent tumor therapeutic effect with 5 times larger ablation zone observed by magnetic resonance (MR) imaging than the microwave alone after 3 days treating. Besides, the tumor is nearly completely ablated and can not be recurrent due to the persistent hyperthermia. Moreover, MSMCs have a good biocompatibility and can be degraded and cleared from the body. It is believed that the MSMC is demonstrated to be a promising multifunctional theranostic agent used for treating the larger tumor via the synergistic therapy of enhanced microwave ablation and transcatheter arterial embolization (TAE).

Fu, C. H_., He, F_., Tan, L. F_., Ren, X. L_., Zhang, W_., Liu, T. L_., Wang, J. Z_., Ren, J_., Chen, X. D_., and Meng, X. W_.,MoS₂ nanosheets encapsulated in sodium alginate microcapsules as microwave embolization agents for large orthotopic transplantation tumor therapy, Nanoscale, 2017, 9, 14846-14853.

Anticancer

Bioresponsive Polyoxometalate Cluster for Redox-Activated Photoacoustic Imaging-Guided Photothermal Cancer Therapy

Although various types of imaging agents have been developed for photoacoustic (PA) imaging, relatively few imaging agents exhibit high selectivity/sensitivity to the tumor microenvironment for on-demand PA imaging and therapy.
Herein, molybdenum-based polyoxometalate (POM) clusters with the highest oxidation state of Mo(VI) (denoted as Ox-POM) were designed as novel agents for redox-activated PA imaging-guided photothermal therapy. Capable of escaping from recognition and capture by the liver and spleen, these renal clearable clusters with ultrasmall size (hydrodynamic size: 1.9 nm) can accumulate in the tumor, self-assemble into larger nanoclusters at low pH, and are reduced to NIR absorptive agents in the tumor microenvironment.
Studies in 4T1 tumor-bearing mice indicated that these clusters could be employed for bioresponsive PA imaging-guided tumor ablation in vivo.
Our finding is expected to establish a new physicochemical paradigm for the design of PA imaging agents based on clusters, bridging the conventional concepts of "molecule" and "nano" in the bioimaging field.

Ni, D., Jiang, D., Valdovinos, H. F., Ehlerding, E. B., Yu, B., Barnhart, T. E., Huang, P., and Cai, W.,Bioresponsive Polyoxometalate Cluster for Redox-Activated Photoacoustic Imaging-Guided Photothermal Cancer Therapy, Nano Lett, 2017, 17, 3282-3289.

MoS₂ Alzheimer's

Molybdenum Disulfide Nanoparticles as Multifunctional Inhibitors against Alzheimer's Disease

The complex pathogenic mechanisms of Alzheimer's disease (AD) include the aggregation of beta-amyloid peptides (Abeta) into oligomers or fibrils as well as Abeta-mediated oxidative stress, which require comprehensive treatment. Therefore, the inhibition of Abeta aggregation and free-radical scavenging are essential for the treatment of AD. Nanoparticles (NPs) have been found to influence Abeta aggregation process in vitro. Herein, we report the inhibition effects of molybdenum disulfide (MoS₂) NPs on Abeta aggregation. Polyvinylpyrrolidone-functionalized MoS₂ NPs were fabricated by a pulsed laser ablation method. We find that MoS₂ NPs exhibit multifunctional effects on Abeta peptides: inhibiting Abeta aggregation, destabilizing Abeta fibrils, alleviating Abeta-induced oxidative stress, as well as Abeta-mediated cell toxicity. Moreover, we show that MoS₂ NPs can block the formation of the Ca²⁺ channel induced by Abeta fibrils in the cell membrane for the first time. Thus, these observations suggest that MoS₂ NPs have great potential for a multifunctional therapeutic agent against amyloid-related diseases.
Han, Q., Cai, S., Yang, L., Wang, X., Qi, C., Yang, R., and Wang, C.,Molybdenum Disulfide Nanoparticles as Multifunctional Inhibitors against Alzheimer's Disease, ACS Appl Mater Interfaces. 2017 Jun 28;9(25):21116-21123. doi: 10.1021/acsami.7b03816. Epub 2017 Jun 14.

THERAPEUTIC

Lung and breast cancer cells

223 Sustainable one-step synthesis of hierarchical microspheres of PEGylated MoS₂ nanosheets and MoO₃ nanorods: Their cytotoxicity towards lung and breast cancer cells

Nanotechnology provides an emerging potent alternate mode of cancer therapy. Nanomaterials dispersion or solubility is of particular concern in utilising their full potential applications in biomedical fields. PEGylation of nanomaterials is considered to provide products with stealth properties, and physiological environment with no obvious adverse effects.

The purpose of this work was to develop a sustainable one-step method for fabrication of hierarchical microspheres of PEGylated MoS₂ nanosheets using a stoichiometric ratio of Mo(VI) and thiourea.

This study further investigated the cytotoxicity of the PEGylated MoS₂ nanosheets towards lung (A549) and breast cancer (MCF-7) cell lines by analysing morphological changes and performing dose-dependent cell proliferation, and cytotoxicity analysis using adenosine 5'-triphosphate (ATP), and lactate dehydrogenase (LDH) assay.

For comparison, MoO₃ nanorods were synthesised by simple chemical route and their cytotoxicity towards lung (A549) and breast cancer (MCF-7) cell lines were checked.

The findings suggested that PEGylated MoS₂ nanosheets have excellent cytotoxicity towards breast cancer (MCF-7) cell lines, and MoO₃ have better cytotoxicity towards lung (A549) cancer cell lines.

This work envisages an accessible foundation for engineering sophisticated biomolecule-MoS₂ nanosheets conjugation due to the defect-rich biocompatible surface, to achieve great versatility, additional functions, and further advances in the biomedical field. (C) 2016 Elsevier B.V. All rights reserved.

Kumar, N., George, B. P. A., Abrahamse, H., Parashar, V., and Ngila, J. C.,Sustainable one-step synthesis of hierarchical microspheres of PEGylated MoS₂ nanosheets and MoO₃ nanorods: Their cytotoxicity towards lung and breast cancer cells, Applied Surface Science, 2017, 396, 8-18.

[PEGylated MoS₂: lipoic acid-terminated polyethylene glycol (LA-PEG) grafted onto the surface of MoS₂ nanoflakes endowing the nanoflakes with high colloidal stability and very low cytotoxicity.

See Wei Feng, Liang Chen, Ming Qin, Xiaojun Zhou, Qianqian Zhang, Yingke Miao, Kexin Qiu, Yanzhong Zhang and Chuanglong He. Flower-like PEGylated MoS2 nanoflakes for near-infrared photothermal cancer therapy. Scientific Reports 5, Article number: 17422 (2015). doi:10.1038/srep17422.]

MoS₂ cancer therapy

Investigation of Thermally Induced Cellular Ablation and Heat Response Triggered by Planar MoS₂-based Nanocomposite

In comparison to conventional tumor treatment methods, photothermal therapy (PTT) is one of the innovative therapeutic strategies that employs light to produce the localized heat for targeted ablation of cancer cells.

Among various kinds of heat generation nanomaterials, transition metal dichalcogenide nanosheets, especially-molybdenum disulfide (MoS₂) have recently been investigated as one of the promising PTT candidates because of their strong absorbance in the near-infrared (NIR) tissue transparency window and excellent photothermal conversion capability.

In line with the great potential of MoS₂-based nanomaterials in biomedical applications, their intrinsic therapeutic performance and corresponding cellular response are required to be continually investigated.

In order to further improve MoS₂-based PTT efficacy and dissect the molecular mechanism during heat stimuli, in this study, we successfully designed a novel and effective PTT platform by integration of MoS₂ nanosheets with peptide-based inhibition molecules to block the function of heat shock proteins (Hsp₉₀), one type of chaperon proteins that play the protective roles in living system against cellular photothermal response.

Such combined nanosystem could effectively induce cell ablation and viability assays indicated approximately five folds higher PTT treatment efficacy (8.8 % viability) than that of MoS₂ itself (48 % viability) upon 808 nm light irradiation.

Moreover, different from the case based on MoS₂ alone that could cause tumor ablation through the process of necrosis, the detailed mechanism analysis revealed the inhibition of Hsp₉₀ could significantly increase the photothermal-mediated apoptosis, hence resulting in remarkable enhancement of photothermal treatment.

Such promising studies provide the great opportunity to better understand the cellular basis of light triggered thermal response. Moreover, they can also facilitate the rational design of new generations of PTT platforms toward future theranostics.

Ariyasu, S_., Mu, J_., Zhang, X_., Huang, Y_., Yeow, E. K_., Zhang, H_., and Xing, B_.,Investigation of Thermally Induced Cellular Ablation and Heat Response Triggered by Planar MoS₂-based Nanocomposite, Bioconjugate chemistry, 2017.

Insulin mimetic

Exposure to sodium molybdate results in mild oxidative stress in Drosophila melanogaster

OBJECTIVES: The study was conducted to assess the redox status of Drosophila flies upon oral intake of insulin-mimetic salt, sodium molybdate (Na₂MoO₄).

METHODS: Oxidative stress parameters and activities of antioxidant and associated enzymes were analyzed in two-day-old D. melanogaster insects after exposure of larvae and newly eclosed adults to three molybdate levels (0.025, 0.5, or 10 mM) in the food.

RESULTS: Molybdate increased content of low molecular mass thiols and activities of catalase, superoxide dismutase, glutathione-S-transferase, and glucose^-6-phosphate dehydrogenase in males. The activities of these enzymes were not affected in females. Males exposed to molybdate demonstrated lower carbonyl protein levels than the control cohort, whereas females at the same conditions had higher carbonyl protein content and catalase activity than ones in the control cohort. The exposure to 10 mM sodium molybdate decreased the content of protein thiols in adult flies of both sexes. Sodium molybdate did not affect the activities of NADP-dependent malate dehydrogenase and thioredoxin reductase in males or NADP-dependent isocitrate dehydrogenase in either sex at any concentration.

DISCUSSION: Enhanced antioxidant capacity in upon Drosophila flies low molybdate levels in the food suggests that molybdate can be potentially useful for the treatment of certain pathologies associated with oxidative stress.

Perkhulyn, N. V_., Rovenko, B. M_., Lushchak, O. V_., Storey, J. M_., Storey, K. B_., and Lushchak, V. I_.,Exposure to sodium molybdate results in mild oxidative stress in Drosophila melanogaster, Redox report : communications in free radical research, 2017, 1-10.

[Drosophila melanogaster = fruit fly. See https://en.wikipedia.org/wiki/Drosophila_melanogaster and Similarity to humans:

“A March 2000 study by National Human Genome Research Institute comparing the fruit fly and human genome estimated that about 60% of genes are conserved between the two species.[32] About 75% of known human disease genes have a recognizable match in the genome of fruit flies,[33] and 50% of fly protein sequences have mammalian homologs. An online database called Homophila is available to search for human disease gene homologues in flies and vice versa.[34] Drosophila is being used as a genetic model for several human diseases including the neurodegenerative disorders Parkinson's, Huntington's, spinocerebellar ataxia and Alzheimer's disease. The fly is also being used to study mechanisms underlying aging and oxidative stress, immunity, diabetes, and cancer, as well as drug abuse.”

Antioxidant and associated enzymes. See http://www.news-medical.net/health/Antioxidant-Enzyme-Systems.aspx Enzymes that catalyze reactions to neutralize free radicals and reactive oxygen species: superoxide dismutase, glutathione peroxidise, glutathione reductase, catalases, lipoic acid. They require co-factors such as selenium, iron, copper, zinc, and manganese for optimum catalytic activity.

“These form the body’s endogenous defence mechanisms to help protect against free radical-induced cell damage. The antioxidant enzymes – glutathione peroxidase, catalase, and superoxide dismutase (SOD) – metabolize oxidative toxic intermediates.]

The Production of Medical ISOTOPES without Nuclear Reactors or Uranium Enrichment

This article examines the current capability of accelerator technology, which is rapidly improving, to produce medical isotopes. A detailed analysis of 12 medical isotopes that are in active diagnostic and therapeutic use and typically made in nuclear reactors shows that accelerator-based technologies, such as linear accelerators, cyclotrons, and spallation neutron sources, could meet medical demand for these isotopes, without the use of enriched uranium and with low proliferation risk. The feasibility of accelerator-based production of an additional 70 isotopes that have a potential medical use is also discussed. A simple estimate suggests that accelerators can produce isotopes at a cost comparable to reactors. This article includes four case studies that illustrate the recent choices that emerging market countries have made when expanding domestic medical isotope production. Technical, commercial, and regulatory steps for commercialization are also described. The article concludes with policy suggestions that would increase the adoption of accelerator-based medical isotope production.

Hoedl, S. A., and Updegraff, W. D.,The Production of Medical Isotopes without Nuclear Reactors or Uranium Enrichment, Science & Global Security, 2015, 23, 121-153.

Synthesis, Structural Characterization and Preliminary Biological Studies of Several Heterocyclic Transition Metal CARBONYL COMPLEXES

The reaction of molybdenum, tungsten and manganese carbonyls with several thiazole heterocycle ligands yielded a number of coordinated transition metal complexes 1-10. Of these complexes 16 are new compounds which have not been reported to date. The structures of new compounds were characterized by FT-IR and H-1-NMR spectroscopy as well as single-crystal X-ray diffraction analysis. Complexes 1-10 are carbon monoxide releasing molecules that show structure-related anti-cancer activity. The cytotoxicity of all compounds on Hela cells was evaluated by MTT assay, and the results show that carbon monoxide releasing molecules containing such Schiff base ligands may have biomedical applications for their anti-tumor effect.

Hu, S. F., Cui, X. W., He, W. M., Chen, X. Y., Gu, Z. K., Zhao, J. Z., Zeng, G., Shi, Z., Zhu, L., and Nie, H. M.,Synthesis, Structural Characterization and Preliminary Biological Studies of Several Heterocyclic Transition Metal Carbonyl Complexes, Zeitschrift Fur Anorganische Und Allgemeine Chemie, 2015, 641, 2452-2459.

The Biochemical Role of Macro and Micro-Minerals in the Management of DIABETES MELLITUS and its Associated Complications: A Review

Diabetes mellitus is a chronic physiological glucose metabolic disorder. Its high prevalence globally has a significant impact on the quality of life. The management of diabetes includes non-pharmacological and glucose lowering agents. Although these methods are effective, they have drawbacks. This has led to a search for alternative therapy in macro and micro-minerals from dietary foods and plants. There is therefore a need to review, identify and classify their modes of action in diabetes mellitus therapy.

Materials and Methods: This review was carried out using comprehensive literature reports on the use of mineral elements in the management of diabetes. Empirical online searches were conducted for different elements that have been studied for their anti-diabetic potentials both in vivo and in vitro. The University of Fort Hare's online database was also used.

Results and Discussion: The results indicate that magnesium, molybdenum, zinc, vanadium and manganese facilitate glucose catabolism. Chromium, vanadium, zinc, molybdenum and magnesium can enhance insulin activity while molybdenum, manganese and zinc stimulate lipogenesis. Zinc and iron can modulate glucose, metabolizing enzymes in the gastrointestinal tract and limit oxidative stress, respectively. These agents have similar mechanisms to conventional drugs in ameliorating diabetic status and other associated complications. Conclusion: The mechanisms of these elements are well known, however, the synergetic effects of their combinations are still obscure. Literature on their safe dose(s) is still scanty. Evaluation of other useful macro and micro-minerals should also be undertaken. It is envisaged that the use of mineral supplements will promote good health in diabetics.

Kibiti, C. M., and Afolayan, A. J.,The Biochemical Role of Macro and Micro-Minerals in the Management of Diabetes Mellitus and its Associated Complications: A Review, International Journal for Vitamin and Nutrition Research, 2015, 85, 88-103.

[Lipogenesis is the process by which acetyl-CoA is converted to fatty acids. Acetyl-CoA is an intermediate stage in metabolism of simple sugars, such as glucose, a source of energy of living organisms. Through lipogenesis and subsequent triglyceride synthesis, the energy can be efficiently stored in the form of fats. https://en.wikipedia.org/wiki/Lipogenesis.]

Application of computational models to estimate organ radiation dose in rainbow trout from uptake of MOLYBDENUM-99 with comparison to iodine-131

This study compares three anatomical phantoms for rainbow trout (Oncorhynchus mykiss) for the purpose of estimating organ radiation dose and dose rates from molybdenum-99 (Mo-99) uptake in the liver and GI tract. Model comparison and refinement is important to the process of determining accurate doses and dose rates to the whole body and the various organs. Accurate and consistent dosimetry is crucial to the determination of appropriate dose-effett relationships for use in environmental risk assessment. The computational phantoms considered are (1) a geometrically defined model employing anatomically relevant organ size and location, (2) voxel reconstruction of internal anatomy obtained from CT imaging, and (3) a new model utilizing NURBS surfaces to refine the model in (2). Dose Conversion Factors (DCFs) for whole body as well as selected organs of O. mykiss were computed using Monte Carlo modeling and combined with empirical models for predicting activity concentration to estimate dose rates and ultimately determine cumulative radiation dose (mu Gy) to selected organs after several half-lives of Mo-99. The computational models provided similar results, especially for organs that were both the source and target of radiation (less than 30% difference between all models). Values in the empirical model as well as the 14 day cumulative organ doses determined from Mo-99 uptake are compared to similar models developed previously for I-131. Finally, consideration is given to treating the GI tract as a solid organ compared to partitioning it into gut contents and GI wall, which resulted in an order of magnitude difference in estimated dose for most organs. (C) 2015 Elsevier Ltd. All rights reserved.

Martinez, N. E., Johnson, T. E., and Pinder, J. E.,Application of computational models to estimate organ radiation dose in rainbow trout from uptake of molybdenum-99 with comparison to iodine-131, Journal of Environmental Radioactivity, 2016, 151, 468-479.

Study of ANTITUMOR effect of selected vanadium and molybdenum organometallic complexes in human leukemic T-cells

This work describes cytotoxic effect of non-platinum metal-based compounds on the human T-leukemic cells with different p53 status (p53 wild-type MOLT-4 and p53-deficient Jurkat cells). The cytotoxic and apoptosis-inducing effect of the vanadium complex [(mu₅-C₅H₅)₂v(5-NH₂-phen)]OTf (V1) and molybdenum complex [(mu₃-C₃H₅)Mo(CO)₂(phen)Cl] (Mo1) were studied using flow cytometry, spectrophotometry and Western blotting. We found that the cytotoxic effect of both tested complexes after 24 h is higher against the both examined cell lines than that of cis-platin (cis-DDP). At later investigated time intervals of 48 and 72 h, the cytotoxic effect of the cis-DDP increased but the values of the cytotoxicity of the tested V1 and Mol complexes remained unchanged, with the cytotoxicity of V1 comparable to that of cis-DDP. Furthermore we observed that the apoptotic process was induced by the activation of the caspases 9 (intrinsic pathway) and 8 (extrinsic pathway) in cells exposed to evaluated complexes. In case of the p53 wild-type MOLT-4 cells, the expression of the tumor-suppressor protein p53 and its form phosphorylated at the serine 15 increased after both V1 and Mo1 treatment, similar to the effect of cis-DDP. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

Sebestova, L_., Havelek, R_., Rezacova, M_., Honzicek, J_., Krocova, Z_., and Vinklarek, J_.,Study of antitumor effect of selected vanadium and molybdenum organometallic complexes in human leukemic T-cells, Chemico-Biological Interactions, 2015, 242, 61-70.

Molybdenum disulphide. Injectable 2D MoS -Integrated Drug Delivering Implant for Highly Efficient NIR-Triggered Synergistic Tumor Hyperthermia

MoS₂ nanosheets and a doxorubicin (DOX)-containing poly (lactic-co-glycolic acid) (PLGA)/ MoS₂ /DOX composite implant is successfully constructed based on the unique phase-changing behavior of PLGA/ MoS₂ /DOX oleosol within tumors. The fast phase transformation can firmly restrict MoS₂ and DOX within tumors, and the integrated MoS₂and DOX can endow the implant with high synergistic photothermal and chemotherapeutic efficiency against tumors.

Wang, S., Chen, Y., Li, X., Gao, W., Zhang, L., Liu, J., Zheng, Y., Chen, H., and Shi, J.,Injectable 2D MoS -Integrated Drug Delivering Implant for Highly Efficient NIR-Triggered Synergistic Tumor Hyperthermia, Advanced materials (Deerfield Beach, Fla.), 2015.

MoS₂ nanoplates. Aptamer loaded MoS₂ nanoplates as nanoprobes for detection of intracellular ATP and controllable photodynamic therapy

In this work we designed a MoS₂ nanoplate-based nanoprobe for fluorescence imaging of intracellular ATP and photodynamic therapy (PDT) via ATP-mediated controllable release of O₂^-1. The nanoprobe was prepared by simply assembling a chlorine e₆ (Ce₆) labelled ATP aptamer on MoS₂ nanoplates, which have favorable biocompatibility, unusual surface-area-to-mass ratio, strong affinity to single-stranded DNA, and can quench the fluorescence of Ce₆. After the nanoprobe was internalized into the cells and entered ATP-abundant lysosomes, its recognition to ATP led to the release of the single-stranded aptamer from MoS₂ nanoplates and thus recovered the fluorescence of Ce₆ at an excitation wavelength of 633 nm, which produced a highly sensitive and selective method for imaging of intracellular ATP. Meanwhile, the ATP-mediated release led to the generation of O^-1(2) under 660 nm laser irradiation, which could induce tumor cell death with a lysosomal pathway. The controllable PDT provided a model approach for design of multifunctional theranostic nanoprobes. These results also promoted the development and application of MoS₂ nanoplate-based platforms in biomedicine.

Jia, L., Ding, L., Tian, J. W., Bao, L., Hu, Y. P., Ju, H. X., and Yu, J. S.,Aptamer loaded MoS₂ nanoplates as nanoprobes for detection of intracellular ATP and controllable photodynamic therapy, Nanoscale, 2015, 7, 15953-15961.

[Aptamers: oligonucleotide or peptide molecules that bind to a specific target molecule. Theranostics: developing specific, individualized therapies for diseases combining diagnostic and therapeutic capabilities into a single agent. Nanoparticle-based theranostic agents www.ncbi.nlm.nih.gov/pmc/articles/PMC2988080/.]

Molybdenum nanoparticles antioxidative and cytoprotective response in human cells

Nanotechnology based therapeutics can offer an alternative platform in a wide variety of biomedical applications. Here we report novel cytotoxicity preventive potential of molybdenum nanoparticles (Mo NPs) in human breast (MCF-7) and fibrosarcoma (HT-1080) cells compromised with oxidant exposure. Physicochemical properties such as size, crystallinity, purity and band gap (an optical characteristic) of Mo NPs were characterized respectively by field emission transmission electron microscopy (FETEM), X-ray diffraction (XRD), energy dispersive spectrum (EDS) and UV-vis absorption spectroscopy. The average size of crystalline Mo NPs was found to be 35 nm with a band gap of 1.4 eV. Potential cytotoxicity of Mo NPs was evaluated by a battery of cell viability and oxidative stress parameters. Cell viability and oxidative stress data suggested Mo NPs to be reasonably non-cytotoxic. Cytotoxic preventive and GSH [glutathione] restoring potential of Mo NPs was determined against cytotoxicity and oxidative stress induced by H₂O₂ (and ZnO NPs) in two cells. Mo NPs significantly increased GSH level in MCF-7 and HT-1080 cells, an activity that was comparable to antioxidant N-acetyl cysteine (NAC). GSH level was increased 1.56 times in MCF-7 cells and 1.25 times in HT-1080 cells by 100 mug/ml of Mo NPs relative to control cells in 24 h. End-point data clearly suggest that Mo NPs significantly protected cells against cytotoxicity induced by H₂O₂ and ZnO (NPs) (p<0.05). Our study warrants further investigation about Mo NPs that could be exploited in myriads of nanotechnology applications.

Akhtar, M. J_., Ahamed, M_., Alhadlaq, H. A_., Alshamsan, A_., Khan, M. A_., and Alrokayan, S. A_.,Antioxidative and cytoprotective response elicited by molybdenum nanoparticles in human cells, Journal of colloid and interface science, 2015, 457, 370-7.

Antitumor effect of selected vanadium and molybdenum organometallic complexes in human leukemic T-cells

This work describes cytotoxic effect of non-platinum metal-based compounds on the human T-leukemic cells with different p53 status (p53 wild-type MOLT-4 and p53-deficient Jurkat cells). The cytotoxic and apoptosis-inducing effect of the vanadium complex [(eta5-C₅H₅)₂V(5-NH₂-phen)]OTf (V1) and molybdenum complex [(eta3-C₃H₅)Mo(CO)₂(phen)Cl] (Mo1) were studied using flow cytometry, spectrophotometry and Western blotting. We found that the cytotoxic effect of both tested complexes after 24 h is higher against the both examined cell lines than that of cis-platin (cis-DDP). At later investigated time intervals of 48 and 72 h, the cytotoxic effect of the cis-DDP increased but the values of the cytotoxicity of the tested V1 and Mo1 complexes remained unchanged, with the cytotoxicity of V1 comparable to that of cis-DDP. Furthermore we observed that the apoptotic process was induced by the activation of the caspases 9 (intrinsic pathway) and 8 (extrinsic pathway) in cells exposed to evaluated complexes. In case of the p53 wild-type MOLT-4 cells, the expression of the tumor-suppressor protein p53 and its form phosphorylated at the serine 15 increased after both V1 and Mo1 treatment, similar to the effect of cis-DDP.

Sebestova, L., Havelek, R., Rezacova, M., Honzicek, J., Krocova, Z., and Vinklarek, J.,Study of antitumor effect of selected vanadium and molybdenum organometallic complexes in human leukemic T-cells, Chemico-biological interactions, 2015, 242, 61-70.

Molybdenum-99 medical radioisotope shortages

Since June 2009, the NEA and its High-level Group on the Security of Supply of Medical Radioisotopes (HLG-MR) have examined the causes of Mo-99 /(99)mTc supply shortages and developed a policy approach, including principles and supporting recommendations to address those causes. The NEA has also reviewed the global Mo-99 /(99)mTc supply situation periodically, using the most up-to-date data from supply chain participants, to highlight periods of reduced supply and underscore the case for implementing the HLG-MR policy approach in a timely and globally-consistent manner. In 2012, the NEA released a Mo-99 supply and demand update for the period up to 2030 (A Supply and Demand Update of the Molybdenum-99 Market, OECD/NEA, 2012), identifying periods of low supply relative to demand. This paper presents the preliminary results from an updated Mo-99 supply and demand forecast, focusing on the potentially critical 2015-2020 period, when two major Mo-99 producers (the NRU reactor in Canada and the OSI-RIS reactor in France). are scheduled to cease 99Mo irradiations. On the demand side, the NM had previously released a study with the results from a global survey of future demand for Mo-99 /(99)mTc (OECD-NEA, 2011), devising a scenario based on a data assessment by an expert advisory group. In the current analysis, the expected demand growth rate and total demand have been modified,,based on the latest information from supply chain participants. On the supply side, the NM has updated the list of current and planned new Mo-99 /(99)mTc irradiation and processing projects. The modelling results incorporate revisions to production start/end dates, potential additional projects, and impacts of converting to the use of low-enriched uranium (LEU) targets on Mo-99 /(99)mTc capacity and production. The supply forecast horizon (2015 to 2020) has been chosen to reflect upcoming, important changes in global production capacity the planned shutdowns in Canada and France, and the expected commissioning of new reactor- and non-reactor-based projects in Europe, the United States, South America, and Australia

Peykov, P. and Cameron, R., Are Radioisotope Shortages a Thing of the Past?, Atw-International Journal for Nuclear Power, 2014, 59, 551-+.

Treatment of anaemia

Magnesium molybdate in daily doses of 0.06-0.20 g Mo has been used in the treatment of various conditions including anaemia and as a general tonic for restoring appetite after convalescence [Vignoli and Defretin, 1963].

Vignoli L.and Defretin, J. P., Biologie medicale, 1963, 52, 319.

A sustained-release preparation of a molybdenised iron(II) sulfate is capable of promptly correcting iron deficiency anaemia and is prescribed for this purpose [Mouratoff and Batterman, 1961; Stevenson, 1962; Rudolph et al., 1963].

Mouratoff, G. L. and Batterman, R. C., J. New Drugs, 1961,1,157.
Stevenson, T. D., Current Therapeutic Research, 1962, 4, 107.
Rudolph, I., Ongchangco, M. N. and Fink, H., Current Therapeutic Research, 1963, 5, 517.

Prevention of dental caries

It is well known that fluoride is effective against the development of dental caries in experimental animals and in human beings. There is evidence that trace elements, particularly molybdenum, in the water supply and in food, enhance the cariostatic effect of fluoride [Schutte, 1964]. For example, children fed on vegetables from the molybdenum-rich Napier area of New Zealand had fewer caries than children from other areas. Similar epidemiological studies in Europe and the United States have confirmed the cariostatic effect of molybdenum [Lossee and Bibby, 1970; Hadjimarkos, 1966; Anderson, 1969; Jenkins, 1967; Lossee and Adkins, 1971].

Schutte, K. H., The Biology of the Trace Elements, Crosby Lockwood and Son Ltd., London, 1964, 92.
Lossee, F. L. and Bibby, B. G., New York State Dental Journal, 1970, 36, 15.
Hadjimarkos, D. M., Anderson, R. J., Caries Res., 1969, 3, 75.
Arch. Environ. Health, 1966, 13, 102.
Jenkins, G., British Dental Journal, 1967, 435, 500, 545.
Lossee, F. L. and Adkins, B. L., Geol. Soc. Amer., Mem., 1971, 123, 203.

The incidence of dental caries is lower in parts of Hungary than would be expected from the fluoride content of the water supply. On investigation it was found that the molybdenum content of the drinking water was high. Further studies from New Zealand, from the cities of Hastings and Napier, showed that the incidence of caries in Napier was significantly less than in Hastings, although both towns had the same water supply. However, the inhabitants of Napier ate vegetables grown in soil that had been under the sea until raised by an earthquake 30 years ago; the concentration of molybdenum was much higher in this soil than in that around Hastings. The molybdenum content of the teeth of boys living in Napier was higher than that of boys in Hastings, although the hair content of molybdenum in boys from both cities was the same. Another piece of evidence suggesting that deficiency of molybdenum plays a part in dental caries is that in Somerset UK the incidence of caries is high in children from areas where the cattle suffer from molybdenum deficiency.

Many workers have given molybdenum to animals and confirmed its anti-cariogenic properties, although in some cases the dose of molybdenum was high. It is not yet established what is the effective anti-cariogenic dose of molybdenum, at what stage in tooth formation it acts, or whether there is any relation between fluoride and molybdenum. Molybdenum has been shown to reduce the solubility of teeth in acid and also to reduce the acid output by the salivary glands. It is more likely that molybdenum acts by affecting the morphology of teeth than by other mechanisms. There is an additive effect between the benefits of fluoride and molybdenum, though fluoride is undoubtedly the more important. Molybdenum increases the absorption of fluoride from the stomach.

The route by which molybdenum reached individuals living in areas of molybdenum-rich soils was through locally produced and consumed vegetables and especially milk [Anderson, 1969]. Water supplies do not make an important contribution to the daily intake of molybdenum [Hadjimarkos, 1966]. The effect of molybdenum and other trace elements on the development of dental caries in experimental animals has been studied [Navia, 1970; Bertrand et al., 1972; Helsby, 1973]. Molybdenum and also vanadium and strontium were mildly cariostatic. There are indications that ammonium molybdate, (NH₄)₂MoO₄, is cariostatic but that ammonium heptamolybdate, (NH₄)₆Mo₇O_24.4H₂O, is not [Jenkins, 1967]. The enamel of rat teeth formed in the presence of molybdenum and fluoride has been examined by electron microscopy [Kruger, 1969]. Both elements influence mineralisation. The cariostatic effect of molybdenum is well established and there is need for more research, especially on the mechanism of its action, the level required, and the method of administration.

Hadjimarkos, 1966; Anderson, 1969; Jenkins, 1967; Lossee and Adkins, 1971].
Navia, J. M., Advan. Chem. Ser., 1970, 94, 123.
Bertrand, G., Blanquet, P. and Laparra, J. C. R. Soc. Biol., 1972, 166, 353.
Helsby, C. A., Caries Res., 1973, 7, 332.
Jenkins, G., British Dental Journal, 1967, 435, 500, 545.
Kruger, B. J., J. Dent. Res., 1969, 48, 1303.

Effect of molybdenum on the immunological reactivity of organisms

The addition of molybdenum as an aqueous solution of ammonium molybdate in amounts of 50-250 mg/kg to the diet of rabbits daily for up to 12 months increased the immunological reaction towards Bact. proteus OX19 culture. The optimum dose was 250 mg/kg when the amount of antibodies and phagocytes was two to three times higher than in control animals [Devyatka et al., 1971].

Devyatka, D. G., Val'chuk, N. K., Voronina, T. Z. and Bukhovets, V. J., Gig. Sanit., 1971, 36, 104.

Molybdenum and cancer

For a review see

Metal passivity as mechanism of metal carcinogenesis: Chromium, nickel, iron, copper, cobalt, platinum, molybdenum, CORNELIA RICHARDSON-BOEDLER Toxicological & Environmental Chemistry, Jan–Mar 2007; 89(1): 15–70.

There are indications of a relationship between molybdenum deficiency and the development of various tumours. The incidence of oesophageal cancer in areas of South Africa varies depending on location [Davies, 1975; Rose, 1968; Burrell et al., 1966]. The gardens of a group of Bantu women who died of cancer were less fertile and less productive than those of tumour-free women. Severe signs of molybdenum deficiency were noted in plants grown in gardens of the cancer sufferers. It is suggested that the molybdenum deficiency resulted in the plants being more prone to attack by fungi, e.g. Aspergillus flavus, which has been implicated as a cause of liver cancer in animals. The distribution of molybdenum in mouse liver and Sarcoma 180 was determined following the intraperitoneal injection daily for 6 d of various molybdenum compounds [Caruthers and Regelson, 1963]. With Na₄SiMo_l2O₄₀, MoCl₅, and MoBr₂ there was an accumulation of molybdenum in the liver and the tumour but with (NH₄)₆Mo₇O₂₄.4H₂O and Mo₃(H₂C₂O₄).2H₂O there was no such accumulation. The copper and zinc contents of the liver and the tumour were not affected by any of the molybdenum compounds nor was the growth rate of the tumour. It is possibly relevant that the concentration of xanthine oxidase is relatively low in various tumours and that tumour growth in mice was decreased by treatment with xanthine oxidase concentrates [Bray, 1963].

Davies, I. J. T., Intake (British Medical Journal. Advertiser's Supplement), 1975, 39, 4.
Rose, E. F., Cancer Research, 1968, 28, 2390.
Burrell, R. J. W., Roach, W. A. and Shadwell, A., J. Nat. Cancer Inst., 1966, 36, 201, 211.
Caruthers C.and Regelson, W.,Oncologia, 1963, 16, 101.
Bray, R. C., in The Enzymes, ed. Boyer, P. D., Hardy, L. and Myrback, K., Academic Press, New York, 2nd Edn., 1963, 7, 533.

Structures, DNA binding, DNA cleavage, and antitumor investigations of a series of molybdenum(VI) complexes with some N(4) methyl and ethyl thiosemicarbazone ligands
Four dioxomolybdenum(VI) complexes were synthesized by reaction of [MoO2(acac)2] with thiosemicarbazones derived from 5-allyl-2-hydroxy-3-methoxybenzaldehyde (1), 2-hydroxynaphthaldehyde (2), 2,3-dihydroxybenzaldehyde (3), or 5-tert-butyl-2-hydroxybenzaldehyde (4).

The ligands were coordinated to molybdenum as tridentate ONS donors. X-ray crystallography showed that the distorted octahedral coordination of molybdenum is completed by methanol (D) in 1a, 3a, and 4a or H2O in 2a. The molecular structures of 1, 3, and 4, and the complexes were determined by single-crystal X-ray crystallography.

Binding of the ligand and complexes with calf thymus DNA were investigated by UV, fluorescence titrations, and viscosity measurements.

Gel electrophoresis revealed that all the complexes can cleave pBR322 plasmid DNA.
The cytotoxic properties of the complexes against human colorectal (HCT 116) cell line showed strong antiproliferative activities in relative order 4a > 3a > 1a > 2a with IC50 values of 1.6, 4.0, 4.8, and 6.7 mu M, respectively.

The complexes exhibited more activity than the standard reference drug, 5-fluorouracil (IC50 7.3 mu M).
These studies show that dioxomolybdenum(VI) complexes have potential use in chemotherapy

Hussein, M. A., Guan, T. S., Haque, R. A., Ahamed, M. B. K., and Majid, A. M. S. A., Structures, DNA binding, DNA cleavage, and antitumor investigations of a series of molybdenum(VI) complexes with some N(4) methyl and ethyl thiosemicarbazone ligands, Journal of Coordination Chemistry, 2014, 67, 714-727Water soluble molybdenocene complexes: Synthesis, cytotoxic activity and binding studies to ubiquitin by fluorescence spectroscopy, circular dichroism and molecular modeling
Four new molybdenocene complexes, Cp2Mo(L-ascorbato), Cp2Mo(6-O-palmitoyl-L-ascorbato), [Cp2Mo(ethyl maltolato)]Cl and Cp2Mo((2S)-2-amino-3-methyl-3-thiolato-butanoato), were synthesized and structurally characterized by standard analytical methods.

The cytotoxicity of these complexes was assessed on colon HT-29 and breast MCF-7 cancer cell lines using the 3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyltetrazolium bromide (MTT) assay.

A higher cytotoxic activity was shown by all the new complexes on the MCF-7 cells over the Cp2MoCl2 complex.
The complexes Cp2Mo(L-ascorbato), Cp2Mo(6-O-palmitoyl-L-ascorbato) and [Cp2Mo(ethyl maltolato)]Cl displayed a stronger cytotoxic activity on colon cancer HT-29 cell line, over the molybdenocene dichloride (Cp2MoCl2).

In contrast, Cp2Mo((2S)-2-amino-3-methyl-3-thiolato-butanoato) exhibited proliferative properties on this cell line.
Ubiquitin (Ub)-molybdenocene interactions were investigated using cyclic voltammetry, fluorescence quenching spectroscopy, circular dichroism (CD) and molecular modeling. The thermodynamic parameters (Delta H and Delta S) obtained using fluorescence quenching spectra and van't Hoff plot indicate the Ub-molybdenocene interactions are mainly hydrophobic. The CD data also support hydrophobic interactions with conformational changes in the Ub protein. Docking studies using molecular modeling revealed the amino adds involved in the Ub-molybdenocene interactions and corroborated the hydrophobic nature of the binding combined with hydrogen bonding. (C) 2013 Elsevier Inc All rights reserved

Narvaez-Pita, X., Ortega-Zuniga, C., Acevedo-Morantes, C. Y., Pastrana, B., Olivero-Verbel, J., Maldonado-Rojas, W., Ramirez-Vick, J. E., and Melendez, E., Water soluble molybdenocene complexes: Synthesis, cytotoxic activity and binding studies to ubiquitin by fluorescence spectroscopy, circular dichroism and molecular modeling, Journal of Inorganic Biochemistry, 2014, 132, 77-91.Low Cytotoxicity of Inorganic Nanotubes and Fullerene-Like Nanostructures in Human Bronchial Epithelial Cells: Relation to Inflammatory Gene Induction and Antioxidant Response
The cytotoxicity of tungsten disulfide nano tubes (INT-WS2) and inorganic fullerene-like molybdenum disulfide (IF-MoS2) nanoparticles (NPs) used in industrial and medical applications was evaluated in comparison to standard environmental particulate matter.

The IF-MoS2 and INT-WS2 reside in vesicles/inclusion bodies, suggestive of. endocytic vesicles. In cells representing the respiratory, immune and metabolic systems, both IF-MoS2 and INT-WS2 NPs remained nontoxic compared to equivalent concentrations (up to 100 mu g/mL in the medium) of silica dioxide (SiO2), diesel engine-derived and carbon black NPs, which induced cell death.

Associating with this biocompatibility of IF-MoS2INT-WS2, we demonstrate in nontransformed human bronchial cells (NL-20) relative low induction of the pro-inflammatory cytokines IL-1 beta, IL-6, IL-8, and TNF-alpha.
Moreover, IF-MoS2 and INT-WS2 activated antioxidant response as measured by the antioxidant response element (ARE) using a luciferase reporter, and induced Nrf2-mediated Phase II detoxification genes.
Collectively, our findings suggest that the lower cytotoxicity of IF-MoS2 and INT-WS2 NPs does not reflect general biological inertness. Rather, compared to other NP's, it likely results from decreased proinflammatory activation, but a comparable significant capacity to induce protective antioxidant/detoxification defense mechanisms

Pardo, M., Shuster-Meiseles, T., Levin-Zaidman, S., Rudich, A., and Rudich, Y., Low Cytotoxicity of Inorganic Nanotubes and Fullerene-Like Nanostructures in Human Bronchial Epithelial Cells: Relation to Inflammatory Gene Induction and Antioxidant Response, Environmental Science & Technology, 2014, 48, 3457-3466

Anticancer Activity of Metal Complexes: Involvement of Redox Processes

Cells require tight regulation of the intracellular redox balance and consequently of reactive oxygen species for proper redox signaling and maintenance of metal (e. g., of iron and copper) homeostasis. In several diseases, including cancer, this balance is disturbed. Therefore, anticancer drugs targeting the redox systems, for example, glutathione and thioredoxin, have entered focus of interest. Anticancer metal complexes (platinum, gold, arsenic, ruthenium, rhodium, copper, vanadium, cobalt, manganese, gadolinium, and molybdenum) have been shown to strongly interact with or even disturb cellular redox homeostasis. In this context, especially the hypothesis of "activation by reduction" as well as the "hard and soft acids and bases" theory with respect to coordination of metal ions to cellular ligands represent important concepts to understand the molecular modes of action of anticancer metal drugs. The aim of this review is to highlight specific interactions of metal-based anticancer drugs with the cellular redox homeostasis and to explain this behavior by considering chemical properties of the respective anticancer metal complexes currently either in (pre)clinical development or in daily clinical routine in oncology. Antioxid. Redox Signal. 15, 1085-1127

Jungwirth, U., Kowol, C. R., Keppler, B. K., Hartinger, C. G., Berger, W., and Heffeter, P., Anticancer Activity of Metal Complexes: Involvement of Redox Processes, Antioxidants & Redox Signaling, 2011, 15, 1085-1127.

Two randomised nutrition intervention trials were conducted in Linxian, an area of north central China with some of the world's highest rates of oesophageal and stomach cancer and a population with a chronically low intake of several nutrients. to assess the effects in nearly 30 000 participants of daily supplementation with: retinol and zinc; riboflavin and niacin; vitamin C and molybdenum; and beta-carotene, alpha-tocopherol, and selenium. The second trial provided daily multiple vitamin-mineral supplementation; or placebo in 3318 persons with oesophageal dysplasia, a precursor to oesophageal cancer. After supplements were given for 5.25 y in the general population trial, small but significant reductions in total relative risk [(RR) = 0.91] and cancer (RR = 0.87) mortality were observed in subjects receiving beta-carotene, alpha-tocopherol, and selenium but not the other nutrients. The largest reductions were for cerebrovascular disease mortality, but the effects differed by sex: a significant reduction was observed in men (RR = 0.45) but not women (RR = 0.90).Restoring adequate intake of certain nutrients may help to lower the risk of cancer and other diseases in this high-risk population [Blot et al., 1995].

Blot, W.J., Li, J.Y., Taylor, P.R., Guo, W.D., Dawsey, S.M., Li, B.,. The Linxian Trials - Mortality-Rates By Vitamin-Mineral Intervention Group, American Journal Of Clinical Nutrition,1995, 62, S1424-S1426.

Xanthine dehydrogenase (EC 1.1.1.204) is a molybdenum iron-sulfur, flavin hydroxylase involved in purine catabolism. Xanthine dehydrogenase-induces activation of bioreductive agents including chemotherapeutic agents requiring bioreductive activation for their antineoplastic activities. Xanthine dehydrogenase is potentially important as an enzyme targeted in chemotherapeutic regimens is discussed [Pritsos et al., 1994].

Pritsos, C.A., Gustafson, D.l., Xanthine Dehydrogenase And Its Role In Cancer-Chemotherapy, Oncology Research, 1994, 6, 477-481.

The antitumor active molybdocene dichloride Cp₂MoCl₂ formed two stable adducts at pD 6 which were tentatively assigned as a Cp₂Mo-glutathione chelate involving coordination of the cysteine thiol and glycine carboxylate to the molybdenum centre, and a thiol centred 1:2 Cp₂Mo-glutathione complex. The implications for the mechanism of antitumor action of the metallocene dihalides are discussed.

Mokdsi, G. and Harding, M. M., A H-1 NMR study of the interaction of antitumor metallocenes with glutathione, Journal of Inorganic Biochemistry, 2001, 86, 611-616.

Interest in the aqueous, bio-organometallic chemistry of metallocene dihalides has stemmed from the potent antitumor properties of titanocene dichloride, including results from human clinical trials. Key results on the biological chemistry of molybdocene dichloride are reviewed. Under physiological conditions the positively charged monoaquated species Cp₂Mo(OH)(OH₂)⁺, in equilibrium with the dipositively charged dimer Cp₂Mo(mu-OH)₂MoCp₂, is present.Studies of the coordination chemistry of Cp₂MoCl₂with nucleobases, nucleotides, single-stranded and double-stranded oligonucleotides, and calf-thymus DNA have shown that, while simultaneous phosphate(O) and heterocyclic(N) adducts are formed with nucleotides, negligible interaction with DNA occurs under physiological conditions. Cp₂MoCl₂ forms strong, non-labile complexes with deprotonated thiols in amino acids. Molybdocene dichloride is able to catalyse the hydrolysis of activated phosphate esters under physiological conditions, but hydrolysis of unactivated phosphodiesters is only significant at pH 4. Limited antitumor activity results, inhibition studies with protein kinase C and topoisomerase II, structure-activity and cell-uptake studies have provided some insight into possible mechanisms of antitumor action.

Waern, J.B. and Harding, M. M., Bioorganometallic chemistry of molybdocene dichloride, Journal of Organometallic Chemistry, 2004, 689, 4655-4668.

The compounds molybdenocene dichloride (Cp₂MoCl₂) and [Cp₂Mo(L)(n)]Cl₂ (n = 1, L = 6-mercaptopurine, 6- mercaptopurineribose, 2-amine-6-mercaptopurine and 2-amine-6- mercaptopurineribose and n = 2, L = D-penicillamine) have antitumour properties. Their complexes with calfthymus DNA have been investigated by cyclic voltammetry. (Cp₂MoCl₂) and [Cp₂Mo(L)(n)]Cl₂ (n = 1, L = 2-amine-6- mercaptopurine and 2-amine-6-mercaptopurineribose and n = 2, L = D-penicillamine) complexes showed weak DNA bindings (3.2- 10.1%) while the complexes containing the ligands 6- mercaptopurine and 6-mercaptopurineribose showed negligible interactions.

Rodriguez, M.I., Chavez-Gil, T., Colon, Y., Diaz, N., and Melendez, E., Molybdenocene-DNA interaction studies using electrochemical analysis, Journal of Electroanalytical Chemistry, 2005, 576, 315-322.

Mo and cancer molybdenocene

In the range 4 <=, pD <=, 9 by NMR spectroscopy the ribonucleosides and ribonucleoside monophosphates uridine, adenosine, cytidine, guanosine, 5'-UMP, 5'-AMP, 5'-CMP and 5'-GMP bind Cp₂Mo²⁺ exclusively through the ribose moiety giving rise to the chelate complexes [Cp₂Mo(urd-O2',O3')], [Cp₂Mo(ade-O2',O3')], [Cp₂Mo(cyd-O2',O3')], and [Cp₂Mo(gua-O2',O3')]. The ribonucleotides form three types of complex with Cp₂Mo²⁺ in neutral solution, namely N,PO-macrochelates, PO,O3'-coordinated species as well as O2',O3'-chelates, while at pD 9 only sugar coordination is observed.

Erxleben, A. and Yovkova, L., Reaction behavior of molybdocene dichloride towards ribonucleosides and ribonucleoside monophosphates: Rare example of sugar coordination, Inorganica Chimica Acta, 2006, 359, 2350-2360.
Waern, J.B., Harris, H. H., Lai, B., Cai, Z. H., Harding, M. M., and Dillon, C. T., Intracellular mapping of the distribution of metals derived from the antitumor metallocenes, Journal of Biological Inorganic Chemistry, 2005, 10, 443-452.

Bioorganometallic chemistry of molybdenocene dichloride and its derivatives: cancer therapy

The potential application of metallocene complexes into the cancer research was established by the pioneer work of Kopf-Maeir and Kopf in the late 1970s. The combination of organometallic chemistry and biochemistry created a new research area: bioorganometallic chemistry. Bioorganometallic chemistry has developed rapidly in the last thirty years leading to application of organometallic species into diagnostic, sensors, immunoassays and anticancer research among others. This review focuses on the bioorganometallic chemistry of molybdenocene dichloride and its derivatives as metal-based anticancer drugs. The anticancer properties of molybdenocene dichloride and its derivatives are described as well as the mechanism of action, aqueous and coordination chemistry, and molybdenocene-biomolecule interactions. (C) 2012 Elsevier B. V. All rights reserved

Melendez, Enrique, Bioorganometallic chemistry of molybdenocene dichloride and its derivatives, Journal of Organometallic Chemistry, 2012, 706, 4-12.

Molybdocene is cytotoxic

In V79 Chinese hamster lung cells Cp₂MoCl₂ produced significant genotoxic damage: 0.2 micronuclei/1000 binucleated cells were induced per mu M of Cp₂MoCl₂. Distinct morphological alterations of the nuclei, condensation of chromatin, and a high incidence of polynucleated cells were observed. Implications for the mechanism of antitumor action of molybdocene dichloride are discussed. (c)

Campbell, K. S., Foster, A. J., Dillon, C. T., and Harding, M. M., Genotoxicity and transmission electron microscopy studies of molybdocene dichloride, Journal of Inorganic Biochemistry, 2006, 100, 1194-1198.

Anti-cancer activity of molybdophosphate: heteropoly Mo

The review includes a useful account of the biochemical activity of molybdenum heteropoly compounds, specifically 12-molybdophosphoric acid, and applications as biomedical agents: antitumoral, anticoagulant, antibacterial, antiviral activity. The antitumour activity of molybdophosphoric acid in in vitro tests on human cervix carcinoma cells was low and less than the activity of tungstophosphoric acid. Molybdophosphoric acid did not damage red blood cells. Molybdophosphoric caused a slight increase of the coagulation time of human blood plasma (49 s compared with 40 s) but less than tungstophosphoric acid (100 s). The polyoxometallates did not exhibit antibacterial activity or antiviral activity on plant viruses.

Mioc, U. B., Todorovic, M. R., Davidovic, A., Colomban, P., and Holclajtner-Antunovic, I., Heteropoly compounds - From proton conductors to biomedical agents, Solid State Ionics, 2005, 176, 3005-3017.

Polyoxomolybdate

The polyoxomolybdate hexabis(isopropylammonium) heptamolybdate trihydrate, [NH₃Pri]₆[Mo₇O₂₄].3H₂O (PM-8) suppressed the growth of Co-4 human colon cancer, MX-I human breast cancer and OAT human lung cancer xenografted in nude mice. In an MTS assay DNA ladder formation and detection of apoptotic bodies in nuclei showed that antitumor activity of PM-8 in MKN45 cells was due to apoptosis [programmed cell death]. PM-8 shows promise as a novel anti-cancer agent.

Mitsui, S., Ogata, A., Yanagie, H., Kasano, H., Hisa, T., Yamase, T., and Eriguchi, M., Antitumor activity of polyoxomolybdate, [NH₃Pri]₆[Mo₇O₂₄].3H₂O, against, human gastric cancer model, Biomedicine & Pharmacotherapy, 2006, 60, 353-358.

Prosthetic Metals: Release, Metabolism and Toxicity

03 Evaluation of colonic anastomosis healing using hybrid nanosheets containing molybdenum disulfide (MoS2) scaffold of human placental amniotic membrane and polycaprolactone (PCL) in rat animal model

Epigallocatechin-3-gallate Mo nanoparticles (EGM NPs) efficiently treat liver injury by strongly reducing oxidative stress, inflammation and endoplasmic reticulum stress

MoS2− Decellularized human amniotic membrane reinforced by MoS2Polycaprolactone nanofibers, a novel conductive scaffold for cardiac tissue engineering

MoS2− Molybdenum disulfide MoS2 -based nanostructures for tissue engineering applications: prospects and challenges [Review]

In situ detection of plasma exosomal microRNA for lung cancer diagnosis using duplex-specific nuclease and MoS2 nanosheets

Functionalized MoS2Based Nanomaterials for Cancer Phototherapy and Other Biomedical Applications

Biosafety, Nontoxic Nanoparticles for VL-NIR Photothermal Therapy Against Oral Squamous Cell Carcinoma

MoS2-based nanocomposites for cancer diagnosis and therapy

A Mo(VI) based coordination polymer as an antiproliferative agent against cancer cells

In situ detection of plasma exosomal microRNA for lung cancer diagnosis using duplex-specific nuclease and MoS2 nanosheets

Functionalized MoS2Based Nanomaterials for Cancer Phototherapy and Other Biomedical Applications

Biosafety, Nontoxic Nanoparticles for VL-NIR Photothermal Therapy Against Oral Squamous Cell Carcinoma

MoS2-based nanocomposites for cancer diagnosis and therapy

A Mo(VI) based coordination polymer as an antiproliferative agent against cancer cells

Preparation of cerium molybdates and their antiviral activity against bacteriophage Phi 6 and SARS-CoV-2

Nanomaterials-Based Biosensors for COVID-19 Detection-A Review

Molybdenum-based hetero-nanocomposites for cancer therapy, diagnosis and biosensing application: Current advancement and future breakthroughs

A water-soluble octahedral molybdenum cluster complex as a potential agent for X-ray induced photodynamic therapy

MoS2-based nanocomposites for cancer diagnosis and therapy

Mechanistic insights into the treatment of iron-deficiency anemia and arthritis in humans with dietary molybdenum

Molybdenum trioxide enhances viability, osteogenic differentiation and extracellular matrix formation of human bone marrow-derived mesenchymal stromal cells

A Smart Nanoplatform with Photothermal Antibacterial Capability and Antioxidant Activity for Chronic Wound Healing

The antibacterial activities of MoS2 nanosheets towards multi-drug resistant bacteria

A novel electrochemical lung cancer biomarker cytokeratin 19 fragment antigen 21-1 immunosensor based on Si3N4/MoS2 incorporated MWCNTs and core-shell type magnetic nanoparticles

Targeted Bioimaging of Cancer Cells Using Free Folic Acid-Sensitive Molybdenum Disulfide Quantum Dots through Fluorescence "Turn-Off"

Eradication of Fungi Using MoSe2/Chitosan Nanosheets

Two-dimensional material-based virus detection

Highly sensitive detection of multiple proteins from single cells by MoS2-FET biosensors

Fabrication of MERS-nanovesicle biosensor composed of multi-functional DNA aptamer/graphene- MoS2nanocomposite based on electrochemical and surface-enhanced Raman spectroscopy

Sensory analysis of hepatitis B virus DNA for medicinal clinical diagnostics based on molybdenum doped ZnO nanowires field effect transistor biosensor; a comparative study to PCR test results

Molybdenum Diphosphide Nanorods with Laser-Potentiated Peroxidase Catalytic/Mild-Photothermal Therapy of Oral Cancer

Near-Infrared-Active Copper Molybdenum Sulfide Nanocubes for Phonon-Mediated Clearance of Alzheimer's β-Amyloid Aggregates

VIRUS ANTIVIRAL

Preparation of cerium molybdates and their antiviral activity against bacteriophage Φ6 and SARS-CoV-2

ANEMIA

Mechanistic insights into the treatment of iron-deficiency anemia and arthritis in humans with dietary molybdenum

Two-Dimensional Material-Based Biosensors for Virus Detection

Molybdenum cluster loaded PLGA nanoparticles as efficient tools against epithelial ovarian cancer

Combinatorial discovery of Mo-based polyoxometalate clusters for tumor photothermal therapy and normal cell protection

DNA

Electrochemical detection of cell concentration based on reaction of DNA with molybdate

Biological effects of molybdenum compounds in nanosized forms under in vitro and in vivo conditions

CANCER

Layered MoS2 nanosheets modified by biomimetic phospholipids: Enhanced stability and its synergistic treatment of cancer [therapy] with chemo-photothermal therapy

Case-control study of brain and other central nervous system cancer among workers at semiconductor and storage device manufacturing facilities

A Metallomic approach to assess associations of serum metal levels with gallstones and gallbladder cancer

M. H. Lee, Y. T. Gao, Y. H. Huang, E. E. McGee, T. Lam, B. Wang, M. C. Shen, A. Rashid, R. M. Pfeiffer, A. W. Hsing, and J. Koshiol, A metallomic approach to assess associations of serum metal levels with gallstones and gallbladder cancer, Hepatology, 2020, 71, 917-928

.

Steering efficacy of nano molybdenum towards cancer [therapy]: Mechanism of action

CANCER

Biodegradation-mediated enzymatic activity-tunable molybdenum oxide nanourchins for tumor-specific cascade catalytic therapy

CANCER

Biodegradation-Mediated Enzymatic Activity-Tunable Molybdenum Oxide Nanourchins for Tumor-Specific Cascade Catalytic Therapy

CANCER

Steering Efficacy of Nano Molybdenum Towards Cancer: Mechanism of Action

ANTIBACTERIAL

Dual light-induced in situ antibacterial activities of biocompatibleTiO2/MoS2/PDA/RGD nanorod arrays on titanium

Octahedral molybdenum cluster as a photoactive antimicrobial additive to a fluoroplastic

Antibacterial activity and cytotoxicity of novel silkworm-like nisin@PEGylated MoS2

ALZHEIMER

A disease-modifying treatment for Alzheimer's disease: focus on the trans-sulfuration pathway

THERAPEUTIC

MoO3 CANCER

Steering Efficacy of Nano Molybdenum Towards Cancer: Mechanism of Action

Molybdenum oxide nanoparticles therapy breast cancer

33 Plasmonic MoO3-x nanoparticles incorporated in Prussian blue frameworks exhibit highly efficient dual photothermal/photodynamic therapy

ANTITUMOUR

Molybdenum(II) complexes with p-substituted BIAN ligands: synthesis, characterization, biological activity and computational study

Therapeutic Uses of Molybdenum

Mo NANOCLUSTERS

Synthesis of fluorescent molybdenum nanoclusters at ambient temperature and their application in biological imaging

MoS2 BIOSENSOR CANCER

Highly efficient Polyaniline-MoS2 hybrid nanostructures based biosensor for cancer biomarker detection

MoS2 CANCER

Dual-responsive molybdenum disulfide/copper sulfide-based delivery systems for enhanced chemo-photothermal therapy

THERAPEUTIC

Tumor-Targeted and Biocompatible MoSe2 Nanodots@Albumin Nanospheres as a Dual- Modality Therapy Agent for Synergistic Photothermal Radiotherapy

Molybdenum cofactor deficiency type B knock-in mouse models carrying patient-identical mutations and their rescue by singular AAV injections

Cysteamine functionalized MoS2 quantum dots inhibit amyloid aggregation

MoS₂− Decellularized human amniotic membrane reinforced by MoS₂Polycaprolactone nanofibers, a novel conductive scaffold for cardiac tissue engineering

MoS₂− Molybdenum disulfide MoS₂ -based nanostructures for tissue engineering applications: prospects and challenges [Review]

MoS₂-based nanocomposites for cancer diagnosis and therapy

Eradication of Fungi Using MoSe₂/Chitosan Nanosheets

Highly sensitive detection of multiple proteins from single cells by MoS₂-FET biosensors

Fabrication of MERS-nanovesicle biosensor composed of multi-functional DNA aptamer/graphene- MoS₂nanocomposite based on electrochemical and surface-enhanced Raman spectroscopy

Layered MoS₂ nanosheets modified by biomimetic phospholipids: Enhanced stability and its synergistic treatment of cancer [therapy] with chemo-photothermal therapy

Dual light-induced in situ antibacterial activities of biocompatibleTiO₂/MoS₂/PDA/RGD nanorod arrays on titanium

Antibacterial activity and cytotoxicity of novel silkworm-like nisin@PEGylated MoS₂

MoO₃ CANCER

33 Plasmonic MoO3^-x nanoparticles incorporated in Prussian blue frameworks exhibit highly efficient dual photothermal/photodynamic therapy

MoS₂ BIOSENSOR CANCER

Highly efficient Polyaniline-MoS₂ hybrid nanostructures based biosensor for cancer biomarker detection

MoS₂ CANCER

Tumor-Targeted and Biocompatible MoSe₂ Nanodots@Albumin Nanospheres as a Dual^- Modality Therapy Agent for Synergistic Photothermal Radiotherapy

Cysteamine functionalized MoS₂ quantum dots inhibit amyloid aggregation

Highly efficient Polyaniline- MoS₂ hybrid nanostructures based biosensor for cancer biomarker detection

Antibacterial MoO₃

Skin Cancer MoO₃

Label-free and recalibrated multilayer MoS₂ biosensor for point-of-care diagnostics

Enhancing the colloidal stability and surface functionality of molybdenum disulfide (MoS₂) nanosheets with hyperbranched polyglycerol for photothermal therapy

MoS₂-based sensor for the detection of miRNA in serum samples related to breast cancer

MoS₂ nanosheets encapsulated in sodium alginate microcapsules as microwave embolization agents for large orthotopic transplantation tumor therapy

MoS₂ Alzheimer's

223 Sustainable one-step synthesis of hierarchical microspheres of PEGylated MoS₂ nanosheets and MoO₃ nanorods: Their cytotoxicity towards lung and breast cancer cells

MoS₂ cancer therapy

Investigation of Thermally Induced Cellular Ablation and Heat Response Triggered by Planar MoS₂-based Nanocomposite