In Vivo Long-Term Biodistribution, Excretion, and Toxicology of PEGylated Transition-Metal Dichalcogenides MS2 (M = Mo, W, Ti) Nanosheets.

Jiali Hao,Xuan Yi,Kai Yang,Teng Liu,Zhuang Liu,Guosheng Song,Liang Cheng

doi:10.1002/advs.201600160

Abstract

With unique 2D structures and intriguing physicochemical properties, various types of transition metal dichalcogenides (TMDCs) have attracted much attention in many fields including nanomedicine. Hence, it is of great importance to carefully study the in vivo biodistribution, excretion, and toxicology profiles of different TMDCs, and hopefully to identify the most promising type of TMDCs with low toxicity and fast excretion for further biomedical applications. Herein, the in vivo behaviors of three representative TMDCs including molybdenum dichalcogenides (MoS2), tungsten dichalcogenides (WS2), and titanium dichalcogenides (TiS2) nanosheets are systematically investigated. Without showing significant in vitro cytotoxicity, all the three types of polyethylene glycol (PEG) functionalized TMDCs show dominate accumulation in reticuloendothelial systems (RES) such as liver and spleen after intravenous injection. In marked contrast to WS2‐PEG and TiS2‐PEG, which show high levels in the organs for months, MoS2‐PEG can be degraded and then excreted almost completely within one month. Further degradation experiments indicate that the distinctive in vivo excretion behaviors of TDMCs can be attributed to their different chemical properties. This work suggests that MoS2, among various TMDCs, may be particularly interesting for further biomedical applications owning to its low toxicity, capability of biodegradation, and rapid excretion.

Highlights

With unique 2D structures and intriguing physicochemical properties, various types of transition metal dichalcogenides (TMDCs) have attracted much attengenerally described as the formula MX2, in which M is the transition metal from groups 4–10 of the periodic table and X is tion in many fields including nanomedicine
Transmission electron microscope (TEM) image (Figure S1, Supporting Information) indicated that the synthesized TMDCs exhibited flake-like structures
We have systemically studied the in vivo biodistribution, excretion, and toxicology profiles of three respective types of TMDCs with surface PEGylation

Summary

Results and Discussion

TMDCs (MoS2, WS2, and TiS2) nanoflakes were synthesized by a high-temperature solution-phase method, TEM images (Figure S1, Supporting Information) have showed the morphologies of MoS2, WS2, and TiS2 nanoflakes. The synthesized MoS2, WS2, and TiS2 were dissolved in 1-methyl-2-pyrrolidinone (NMP) and broken into small and single-layer nanosheets under ultrasonication[36] (Figure 1a). After ultrasonication in NMP, the as-synthesized MoS2/ WS2/TiS2 nanosheets became water-soluble, we have tested the dynamic light scattering (DLS) size distribution of these three nanosheets in water (Figure S3, Supporting Information). Thermogravimetric analysis showed the weight percentages of MoS2, WS2, and TiS2 in the PEGylated samples were determined to be 25.99%, 59.72%, and 46.92% (Figure S4, Supporting Information), respectively. MS2 were synthesized by a high-temperature solutionphase method and broken in NMP under ultrasonication to obtain small nanosheets. UV–vis-NIR spectra of PEGylated TMDC nanosheets all showed strong wide-band NIR absorbance (Figure 1d), with the weight extinction coefficients of MoS2-PEG, WS2-PEG, and TiS2-PEG measured to be 26.36, 23.42, and 22.04 Lg−1 cm−1, respectively, at 808 nm

In Vitro Cytotoxicity Study for PEGylated TMDCs

In Vivo Biodistribution and Clearance Behaviors of PEGylated TMDCs

Conclusions

Experiment Section