Pulmonary toxicity, genotoxicity, and carcinogenicity evaluation of molybdenum, lithium, and tungsten: A review.

Molybdenum, lithium, and tungsten are constituents of many products, and exposure to these elements potentially occurs at work. Therefore it is important to determine at what levels they are toxic, and thus we set out to review their pulmonary toxicity, genotoxicity, and carcinogenicity. After pulmonary exposure, molybdenum and tungsten are increased in multiple tissues; data on the distribution of lithium are limited. Excretion of all three elements is both via faeces and urine. Molybdenum trioxide exerted pulmonary toxicity in a 2-year inhalation study in rats and mice with a lowest-observed-adverse-effect concentration (LOAEC) of 6.6 mg Mo/m3. Lithium chloride had a LOAEC of 1.9 mg Li/m3 after subacute inhalation in rabbits. Tungsten oxide nanoparticles resulted in a no-observed-adverse-effect concentration (NOAEC) of 5 mg/m3 after inhalation in hamsters. In another study, tungsten blue oxide had a LOAEC of 63 mg W/m3 in rats. Concerning genotoxicity, for molybdenum, the in vivo genotoxicity after inhalation remains unknown; however, there was some evidence of carcinogenicity of molybdenum trioxide. The data on the genotoxicity of lithium are equivocal, and one carcinogenicity study was negative. Tungsten seems to have a genotoxic potential, but the data on carcinogenicity are equivocal. In conclusion, for all three elements, dose descriptors for inhalation toxicity were identified, and the potential for genotoxicity and carcinogenicity was assessed.

Controlled decoration of nanoceria on the surface of MoS2nanoflowers to improve the biodegradability and biocompatibility inDrosophila melanogastermodel.

In recent years, nanozymes based on two-dimensional (2D) nanomaterials have been receiving great interest for cancer photothermal therapy. 2D materials decorated with nanoparticles (NPs) on their surface are advantageous over conventional NPs and 2D material based systems because of their ability to synergistically improve the unique properties of both NPs and 2D materials. In this work, we report a nanozyme based on flower-like MoS2nanoflakes (NFs) by decorating their flower petals with NCeO2using polyethylenimine (PEI) as a linker molecule. A detailed investigation on toxicity, biocompatibility and degradation behavior of fabricated nanozymes in wild-typeDrosophila melanogastermodel revealed that there were no significant effects on the larval size, morphology, larval length, breadth and no time delay in changing larvae to the third instar stage at 7-10 d for MoS2NFs before and after NCeO2decoration. The muscle contraction and locomotion behavior of third instar larvae exhibited high distance coverage for NCeO2decorated MoS2NFs when compared to bare MoS2NFs and control groups. Notably, the MoS2and NCeO2-PEI-MoS2NFs treated groups at 100µg ml-1covered a distance of 38.2 mm (19.4% increase when compared with control) and 49.88 mm (no change when compared with control), respectively. High-resolution transmission electron microscopy investigations on the new born fly gut showed that the NCeO2decoration improved the degradation rate of MoS2NFs. Hence, nanozymes reported here have huge potential in various fields ranging from biosensing, cancer therapy and theranostics to tissue engineering and the treatment of Alzheimer's disease and retinal therapy.

Tonoplast-Localized OsMOT1;2 Participates in Interorgan Molybdate Distribution in Rice.

Molybdenum (Mo) is an essential element for plant growth and is utilized by several key enzymes in biological redox processes. Rice assimilates molybdate ions via OsMOT1;1, a transporter with a high affinity for molybdate. However, other systems involved in the molecular transport of molybdate in rice remain unclear. Here, we characterized OsMOT1;2, which shares amino acid sequence similarity with AtMOT1;2 and functions in vacuolar molybdate export. We isolated a rice mutant harboring a complete deletion of OsMOT1;2. This mutant exhibited a significantly lower grain Mo concentration than the wild type (WT), but its growth was not inhibited. The Mo concentration in grains was restored by the introduction of WT OsMOT1;2. The OsMOT1;2-GFP protein was localized to the vacuolar membrane when transiently expressed in rice protoplasts. At the reproductive growth stage of the WT plant, OsMOT1;2 was highly expressed in the 2nd and lower leaf blades and nodes. The deletion of OsMOT1;2 impaired interorgan Mo allocation in aerial parts: relative to the WT, the mutant exhibited decreased Mo levels in the 1st and 2nd leaf blades and grains but increased Mo levels in the 2nd and lower leaf sheaths, nodes and internodes. When the seedlings were exposed to a solution with a high KNO3 concentration in the absence of Mo, the mutant exhibited significantly lower nitrate reductase activity in the shoots than the WT. Our results suggest that OsMOT1;2 plays an essential role in interorgan Mo distribution and molybdoenzyme activity in rice.

Molybdenum derived from nanomaterials incorporates into molybdenum enzymes and affects their activities in vivo.

Many nanoscale biomaterials fail to reach the clinical trial stage due to a poor understanding of the fundamental principles of their in vivo behaviour. Here we describe the transport, transformation and bioavailability of MoS2 nanomaterials through a combination of in vivo experiments and molecular dynamics simulations. We show that after intravenous injection molybdenum is significantly enriched in liver sinusoid and splenic red pulp. This biodistribution is mediated by protein coronas that spontaneously form in the blood, principally with apolipoprotein E. The biotransformation of MoS2 leads to incorporation of molybdenum into molybdenum enzymes, which increases their specific activities in the liver, affecting its metabolism. Our findings reveal that nanomaterials undergo a protein corona-bridged transport-transformation-bioavailability chain in vivo, and suggest that nanomaterials consisting of essential trace elements may be converted into active biological molecules that organisms can exploit. Our results also indicate that the long-term biotransformation of nanomaterials may have an impact on liver metabolism.

Differential Phagocytosis-Based Photothermal Ablation of Inflammatory Macrophages in Atherosclerotic Disease.

Inflammatory macrophage (Mφ)-mediated atherosclerosis is a leading cause of mortality and morbidity worldwide. Photothermal therapy (PTT) has been demonstrated as an efficient strategy in killing target cells, and its application in the treatment of inflammation in atherosclerosis is developing. However, the choice of nanomaterials, mechanisms, and side effects are seldom considered. In this study, semiconductor nanomaterials, that is, MoO2 nanoclusters, were synthesized and used for the first time in PTT for inflammatory Mφ-mediated atherosclerosis. Based on cell differential phagocytosis, the optimum amount of MoO2 and treatment time were selected to exert the maximum ablation effect on Mφ and minimal damage on endothelial cells without requiring additional target or selective groups. Moreover, MoO2-based PTT shows an excellent therapeutic effect on atherosclerosis by eliminating Mφ in animal models, with no significant side effects observed. This study explores a new method of nanotechnology and pharmaceutical development by using and optimizing cost-effective metal oxide nanostructures in the treatment of atherosclerosis and motivates further research on minimizing the side effects of related materials.

"Bottom-up" preparation of MoS2 quantum dots for tumor imaging and their in vivo behavior study.

"Bottom-up" method is a popular approach for the preparation of molybdenum disulfide quantum dots (MoS2 QDs) benefitting from less time consumption and no high-powered sonication required. But the relatively low fluorescent quantum yield of the obtained MoS2 QDs and the rare study about their in vivo behavior stimulate us to do more research in this area. In this paper, we proposed a "bottom-up" hydrothermal method to prepare MoS2 QDs with a quantum yield (QY) of 34.55% by optimizing a series of reaction conditions. The successful fluorescence imaging of tumor cells in vitro and in vivo as well as the systematic in vivo behavior study such as biocompatibility, biodistribution and metabolism route provided the good basis for their wider biomedical applications.

Translocation, biotransformation-related degradation, and toxicity assessment of polyvinylpyrrolidone-modified 2H-phase nano-MoS2.

Nano-MoS2 has been extensively investigated in materials science and biomedicine. However, the effects of different methods of exposure on their translocation, biosafety, and biotransformation-related degradability remain unclear. In this study, we combined the advantages of synchrotron radiation (SR) X-ray absorption near-edge structure (XANES) and high-resolution single-cell SR transmission X-ray microscopy (SR-TXM) with traditional analytical techniques to investigate translocation, precise degraded species/ratio, and correlation between the degradation and toxicity levels of polyvinylpyrrolidone-modified 2H-phase MoS2 nanosheets (MoS2-PVP NSs). These NSs demonstrated different biodegradability levels in biomicroenvironments with H2O2, catalase, and human myeloperoxidase (hMPO) (H2O2 < catalase < hMPO). The effects of NSs and their biodegraded byproducts on cell viability and 3D translocation at the single-cell level were also assessed. Toxicity and translocation in mice via intravenous (i.v.), intraperitoneal (i.p.), and intragastric (i.g.) administration routes guided by fluorescence (FL) imaging were investigated within the tested dosage. After i.g. administration, NSs accumulated in the gastrointestinal organs and were excreted from feces within 48 h. After i.v. injection, NSs showed noticeable clearance due to their decreased accumulation in the liver and spleen within 30 days when compared with that in the i.p. group, which exhibited slight accumulation in the spleen. This work paves the way for understanding the biological behaviors of nano-MoS2 using SR techniques that provide more opportunities for future applications.

Release dynamics of As, Co, and Mo in a biochar treated soil under pre-definite redox conditions.

This study assessed the impact of pre-definite redox potential (EH) on the release dynamics and distribution of As, Co, and Mo between the dissolved and colloidal phases as well as their potential mobility and phytoavailability in the sediment phase of a mining soil treated with rice hull biochar (BC). The experiment was conducted from controlled moderately-reducing to oxidizing conditions using an automated biogeochemical microcosm system. Arsenic and Mo were more abundant in the dissolved phase due to their predominant in potential mobile fractions, while Co was more abundant in the colloidal phase due to its association with Fe-(hydr)oxides. Biochar increased the dissolved and colloidal concentrations of As, the dissolved concentration of Co, and the colloidal concentration of Mo under oxidizing condition. On the other hand, the application of BC decreased the dissolved concentration of Mo and the colloidal concentration of Co in the first redox cycle under reducing-acidic condition, due to lower pH values, and chemistry of sulfide-sulfate and Fe/Mn oxides. The phytoavailability of As and Co were higher than their potential mobility in the sediment phase, while the same trend was not discerned for Mo. The potential mobility and phytoavailability of As and Co were high under oxic-acidic conditions. The potential mobility and phytoavailability of Mo might be increased under oxic condition due to the dissolution of Fe and Mn oxides under lower pH conditions, especially in the BC treated soil. Application of such rice hull BC to soil might stimulate the release of As, Co, and Mo under flooding conditions, which might increase the environmental and health risks in such wetland ecosystems.

A two-generation reproductive toxicity study of sodium molybdate dihydrate administered in drinking water or diet to Sprague-Dawley rats.

In an OECD Test Guideline 416 multigenerational study, groups of 24 male and 24 female Sprague-Dawley rats were administered sodium molybdate dihydrate at 0, 5, 17, or 40 mg molybdenum (Mo)/kg bw/day in the drinking water or 40 mg Mo/kg bw/day in the diet over two generations to assess reproductive toxicity. No adverse effect on reproductive function was observed at any dose level in either generation as indicated by no significant dose-related effect on estrus cycles, sperm parameters, mating, fertility, gestation, litter size, pup survival, growth or postnatal development. Systemic toxicity, including decreased body weight, food consumption (males only) and water consumption, was observed among both sexes given 40 mg Mo/kg bw/day in the diet. Serum levels of Mo and copper were increased in a dose-related manner. The No Observed Adverse Effect Levels (NOAEL) are 17 mg Mo/kg bw/day for systemic toxicity and 40 mg Mo/kg bw/day for reproductive toxicity.

Metabolic disposition of WTX101 (bis-choline tetrathiomolybdate) in a rat model of Wilson disease.

1. WTX101 (bis-choline tetrathiomolybdate) is an investigational copper (Cu)-protein-binding agent developed for the treatment of Wilson disease (WD), a rare genetic disorder caused by mutations in the ATP7B Cu-transporter and resulting in toxic Cu accumulation. 2. Mass balance of a single intravenous WTX101 dose, measured as molybdenum (Mo), was assessed over 168 h in control (Long Evans Agouti [LEA]) and Long-Evans Cinnamon (LEC) rats, a WD model. 3. In LEC rats, Mo was partially excreted (up to 45%); 29% by renal clearance, and faecal clearance, still ongoing at 168 h, accounted for 16%. In contrast, in LEA rats, Mo was almost fully excreted (∼87%); 79% was renally cleared with only 7% faecal excretion. 4. In LEC rats, the proportion of faecal to renal Mo excretion was enhanced (4:6) compared to controls (1:9). 5. Substantially more Mo was found in LEC liver and kidney compared with LEA tissues, in line with tissue Cu distribution. 6. These findings are consistent with the WTX101 mechanism of action: in the WD model, excess Cu is removed from hepatic metallothionein and retained within the stable tetrathiomolybdate-Cu-albumin tripartite complex, preventing tetrathiomolybdate degradation and resulting in less urinary elimination and greater faecal excretion than in controls.

Methylene Blue-Fortified Molybdenum Trioxide Nanoparticles: Harnessing Radical Scavenging Property.

A hybrid nanosystem with impeccable cellular imaging and antioxidant functionality is demonstrated. The microwave irradiation-derived molybdenum trioxide nanoparticles (MoO3 NPs) were surface-functionalized with the cationic dye molecule, methylene blue (MB), which enables superior UV-visible absorbance and fluorescence emission wavelengths potential for bioimaging. The radical scavenging property of the pristine MoO3 NPs and MoO3-MB NPs were studied in vivo using Caenorhabditis elegans as the model system. Heat shock-induced oxidative stress in C. elegans was significantly resolved by the MoO3-MB NPs, in agreement with the in vitro radical scavenging study by electron paramagnetic resonance spectroscopy. Hybrid nanostructures of MoO3-MB demonstrate synergistic benefits in intracellular imaging with intrinsic biocompatibility and antioxidant behavior, which can facilitate application as advanced healthcare materials toward bioimaging and clinical therapeutics.

Changes in the fractionation profile of Al, Ni, and Mo during bioleaching of spent hydroprocessing catalysts with Acidithiobacillus ferrooxidans.

Spent hydroprocessing catalysts are known to contain a variety of potentially toxic metals and therefore studies on the bioavailability and mobility of these metals are critical for understanding the possible environmental risks of the spent catalysts. This study evaluates the different chemical fractions/forms of aluminium (Al), nickel (Ni), and molybdenum (Mo) in spent hydroprocessing catalyst and the changes they undergo during bioleaching with Acidithiobacillus ferrooxidans. In the spent catalyst (prior to bioleaching), Al was primarily present in its residual form, suggesting its low environmental mobility. However, Ni comprised mainly an exchangeable fraction, indicating its high environmental mobility. Molybdenum was mainly in the oxidizable form (47.1%), which indicated that highly oxidizing conditions were required to liberate it from the spent catalyst. During bioleaching the exchangeable, reducible and oxidizable fractions of all the metals were leached, whereas the residual fractions remained largely unaffected. At the end of bioleaching process, the metals remaining in the bioleached sample were predominantly in the residual fraction (98.3-99.5%). The 'risk assessment code' (RAC) and IR analysis also demonstrated that the environmental risks of the bioleached residue were significantly lower compared to the untreated spent catalyst. The results of this study suggest that bioleaching is an effective method in removing the metals from spent catalysts and the bioleached residue poses little environmental risk.

Intracellular Mechanistic Understanding of 2D MoS2 Nanosheets for Anti-Exocytosis-Enhanced Synergistic Cancer Therapy.

Emerging two-dimensional (2D) nanomaterials, such as transition-metal dichalcogenide (TMD) nanosheets (NSs), have shown tremendous potential for use in a wide variety of fields including cancer nanomedicine. The interaction of nanomaterials with biosystems is of critical importance for their safe and efficient application. However, a cellular-level understanding of the nano-bio interactions of these emerging 2D nanomaterials ( i. e., intracellular mechanisms) remains elusive. Here we chose molybdenum disulfide (MoS2) NSs as representative 2D nanomaterials to gain a better understanding of their intracellular mechanisms of action in cancer cells, which play a significant role in both their fate and efficacy. MoS2 NSs were found to be internalized through three pathways: clathrin → early endosomes → lysosomes, caveolae → early endosomes → lysosomes, and macropinocytosis → late endosomes → lysosomes. We also observed autophagy-mediated accumulation in the lysosomes and exocytosis-induced efflux of MoS2 NSs. Based on these findings, we developed a strategy to achieve effective and synergistic in vivo cancer therapy with MoS2 NSs loaded with low doses of drug through inhibiting exocytosis pathway-induced loss. To the best of our knowledge, this is the first systematic experimental report on the nano-bio interaction of 2D nanomaterials in cells and their application for anti-exocytosis-enhanced synergistic cancer therapy.

Dietary determinants of urinary molybdenum levels in Mexican women: a pilot study.

OBJECTIVE: This study determined the main dietary sources of urinary molybdenum (Mo) concentrations in a sample of 124 pregnant women in Mexico. MATERIALS AND METHODS: Dietary data was collected during pregnancy, through a semi-qualitative food frequency questionnaire, with information of 84 foods. Urine Mo levels were determined by atomic absorption spectrometry, for at least two trimesters of pregnancy. The associations with Mo levels were estimated by generalized mixed effect regression models. RESULTS: Between 5.8 to 12.7% of the samples were above the 95th percentile of urinary Mo distribution reported by National Health and Nutrition Examination Survey (NHANES) 2009-2010 for women (151 µg/L and 148 µg/g creatinine). After bootstrap resampling was conducted, women with high-consumption of hot peppers (ß=1.34µg/g; 95% CI: 1.00-1.80; p= 0.05) had marginally higher urinary Mo concentration levels, creatinine adjusted, compared to women with low-consumption. CONCLUSION.: Hot chili pepper consumption may contribute to body burden Mo levels in this population.

Dietary determinants of urinary molybdenum levels in Mexican women: a pilot study / Determinantes dietéticos de molibdeno urinario en mujeres mexicanas: un estudio piloto

Abstract: Objective: This study determined the main dietary sources of urinary molybdenum (Mo) concentrations in a sample of 124 pregnant women in Mexico. Materials and methods: Dietary data was collected during pregnancy, through a semi-qualitative food frequency questionnaire, with information of 84 foods. Urine Mo levels were determined by atomic absorption spectrometry, for at least two trimesters of pregnancy. The associations with Mo levels were estimated by generalized mixed effect regression models. Results: Between 5.8 to 12.7% of the samples were above the 95th percentile of urinary Mo distribution reported by National Health and Nutrition Examination Survey (NHANES) 2009-2010 for women (151 μg/L and 148 μg/g creatinine). After bootstrap resampling was conducted, women with high-consumption of hot peppers (β=1.34μg/g; 95% CI: 1.00-1.80; p= 0.05) had marginally higher urinary Mo concentration levels, creatinine adjusted, compared to women with low-consumption. Conclusion. Hot chili pepper consumption may contribute to body burden Mo levels in this population.

Resumen: Objetivo: Determinar las fuentes dietéticas de molibdeno (Mo) urinario en 124 mujeres embarazadas residentes en el estado de Morelos, México. Material y métodos: Mediante un cuestionario de frecuencia de consumo de 84 alimentos, se obtuvo información dietética durante el embarazo. Las concentraciones urinarias de Mo se determinaron por espectrometría de absorción atómica, en al menos dos trimestres del embarazo. La asociación se estimó mediante modelos de efectos mixtos generalizados. Resultados: Entre 5.8 y 12.7% de las muestras superaron el P95 (151 µg/L y 148 µg/g creatinina) de la distribución de Mo urinario reportado para mujeres por la Encuesta Nacional de Nutrición y Salud de Estados Unidos (NHANES) 2009-2010. El mayor consumo de chile (β=1.34μg/g; IC95%: 1.00-1.80; p=0.05) se asoció con concentraciones marginalmente mayores de Mo. Conclusión: Probablemente debido a los fertilizantes o el sistema de riego utilizado en su cultivo, el consumo de chile es una posible fuente de exposición a Mo, en esta población.

Uptake, transport and distribution of molybdenum in two oilseed rape (Brassica napus L.) cultivars under different nitrate/ammonium ratios.

OBJECTIVES: To investigate the effects of different nitrate sources on the uptake, transport, and distribution of molybdenum (Mo) between two oilseed rape (Brassica napus L.) cultivars, L0917 and ZS11. METHODS: A hydroponic culture experiment was conducted with four nitrate/ammonium (NO3-:NH4+) ratios (14:1, 9:6, 7.5:7.5, and 1:14) at a constant nitrogen concentration of 15 mmol/L. We examined Mo concentrations in roots, shoots, xylem and phloem sap, and subcellular fractions of leaves to contrast Mo uptake, transport, and subcellular distribution between ZS11 and L0917. RESULTS: Both the cultivars showed maximum biomass and Mo accumulation at the 7.5:7.5 ratio of NO3-:NH4+ while those were decreased by the 14:1 and 1:14 treatments. However, the percentages of root Mo (14.8% and 15.0% for L0917 and ZS11, respectively) were low under the 7.5:7.5 treatment, suggesting that the equal NO3-:NH4+ ratio promoted Mo transportation from root to shoot. The xylem sap Mo concentration and phloem sap Mo accumulation of L0917 were lower than those of ZS11 under the 1:14 treatment, which suggests that higher NO3-:NH4+ ratio was more beneficial for L0917. On the contrary, a lower NO3-:NH4+ ratio was more beneficial for ZS11 to transport and remobilize Mo. Furthermore, the Mo concentrations of both the cultivars' leaf organelles were increased but the Mo accumulations of the cell wall and soluble fraction were reduced significantly under the 14:1 treatment, meaning that more Mo was accumulated in organelles under the highest NO3-:NH4+ ratio. CONCLUSIONS: This investigation demonstrated that the capacities of Mo absorption, transportation and subcellular distribution play an important role in genotype-dependent differences in Mo accumulation under low or high NO3-:NH4+ ratio conditions.

Optimal Contrast Agent Staining of Ligaments and Tendons for X-Ray Computed Tomography.

X-ray computed tomography has become an important tool for studying the microstructures of biological soft tissues, such as ligaments and tendons. Due to the low X-ray attenuation of such tissues, chemical contrast agents are often necessary to enhance contrast during scanning. In this article, the effects of using three different contrast agents--iodine potassium iodide solution, phosphotungstic acid and phosphomolybdic acid--are evaluated and compared. Porcine anterior cruciate ligaments, patellar tendons, medial collateral ligaments and lateral collateral ligaments were used as the basis of the study. Three samples of each of the four ligament/tendon types were each assigned a different contrast agent (giving a total of twelve samples), and the progression of that agent through the tissue was monitored by performing a scan every day for a total period of five days (giving a total of sixty scans). Since the samples were unstained on day one, they had been stained for a total of four days by the time of the final scans. The relative contrast enhancement and tissue deformation were measured. It was observed that the iodine potassium iodide solution penetrated the samples fastest and caused the least sample shrinkage on average (although significant deformation was observed by the time of the final scans), whereas the phosphomolybdic acid caused the greatest sample shrinkage. Equations describing the observed behaviour of the contrast agents, which can be used to predict optimal staining times for ligament and tendon X-ray computed tomography, are presented.

Biomonitoring Equivalents for molybdenum.

Molybdenum is an essential trace element for mammalian, plant, and other animal systems. The Institute of Medicine (IOM) has established an Estimated Average Requirement (EAR) to assure sufficient molybdenum intakes for human populations; however excessive exposures can cause toxicity. As a result, several agencies have established exposure guidance values to protect against molybdenum toxicity, including a Reference Dose (RfD), Tolerable Daily Intake (TDI) and a Tolerable Upper Intake Level (UL). Biomonitoring for molybdenum in blood or urine in the general population is being conducted by the Canadian Health Measures Survey (CHMS) and the U.S. National Health and Nutrition Examination Survey (NHANES). Using pharmacokinetic data from controlled human dosing studies, Biomonitoring Equivalents (BEs) were calculated for molybdenum in plasma, whole blood, and urine associated with exposure guidance values set to protect against both nutritional deficits and toxicity. The BEEAR values in plasma, whole blood and urine are 0.5, 0.45 and 22 µg/L, respectively. The BEs associated with toxicity range from 0.9 to 31 µg/L in plasma, 0.8-28 µg/L in whole blood and 200-7500 µg/L in urine. These values can be used to interpret molybdenum biomonitoring data from a nutritional and toxicity perspective.

Degradable Molybdenum Oxide Nanosheets with Rapid Clearance and Efficient Tumor Homing Capabilities as a Therapeutic Nanoplatform.

Molybdenum oxide (MoOx) nanosheets with high near-infrared (NIR) absorbance and pH-dependent oxidative degradation properties were synthesized, functionalized with polyethylene glycol (PEG), and then used as a degradable photothermal agent and drug carrier. The nanosheets, which are relatively stable under acidic pH, could be degraded at physiological pH. Therefore, MoOx-PEG distributed in organs upon intravenous injection would be rapidly degraded and excreted without apparent in vivo toxicity. MoOx-PEG shows efficient accumulation in tumors, the acidic pH of which then leads to longer tumor retention of those nanosheets. Along with the capability of acting as a photothermal agent for effective tumor ablation, MoOx-PEG can load therapeutic molecules with high efficiencies. This concept of inorganic theranostic nanoagent should be relatively stable in tumors to allow imaging and treatment, while being readily degradable in normal organs to enable rapid excretion and avoid long-term retention/toxicity.

Smart MoS2/Fe3O4 Nanotheranostic for Magnetically Targeted Photothermal Therapy Guided by Magnetic Resonance/Photoacoustic Imaging.

The ability to selectively destroy cancer cells while sparing normal tissue is highly desirable during the cancer therapy. Here, magnetic targeted photothermal therapy was demonstrated by the integration of MoS2 (MS) flakes and Fe3O4 (IO) nanoparticles (NPs), where MoS2 converted near-infrared (NIR) light into heat and Fe3O4 NPs served as target moiety directed by external magnetic field to tumor site. The MoS2/Fe3O4 composite (MSIOs) functionalized by biocompatible polyethylene glycol (PEG) were prepared by a simple two-step hydrothermal method. And the as-obtained MSIOs exhibit high stability in bio-fluids and low toxicity in vitro and in vivo. Specifically, the MSIOs can be applied as a dual-modal probe for T2-weighted magnetic resonance (MR) and photoacoustic tomography (PAT) imaging due to their superparamagnetic property and strong NIR absorption. Furthermore, we demonstrate an effective result for magnetically targeted photothermal ablation of cancer. All these results show a great potential for localized photothermal ablation of cancer spatially/timely guided by the magnetic field and indicated the promise of the multifunctional MSIOs for applications in cancer theranostics.