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
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.
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, 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.
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-Ce2Mo3O13 exhibited 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 (MoS2-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 (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 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, 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. 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-NH2-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.]