In Vivo Long-term Biodistribution And Toxicology Of PEGylated Transition-metal Dichalcogenides Nanosheets

With unique two-dimensional 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, we systematically investigated the in vivo behaviors of three representative TMDCs including molybdenum dichalcogenides（MoS₂）, tungsten dichalcogenides（WS₂）, and titanium dichalcogenides（TiS₂） nanosheets. Without showing significant in vitro cytotoxicity, all the three types of polyethylene glycol（PEG） functionalized TMDCs showed dominate accumulation in reticuloendothelial systems（RES） such as liver and spleen after intravenous injection. Interestingly, in marked contrast to WS₂-PEG and TiS₂-PEG, which showed high levels of retained metal elements in the mouse organs for months, MoS₂-PEG could be degraded and then excreted almost completely within one month, via both renal and fecal pathways. Further degradation experiments indicated that the distinctive in vivo excretion behaviors of TDMCs could be attributed to their different chemical properties under gradual oxidization. No obvious toxicity of those PEGylated TMDCs was found to the treated mice at our tested dose, despite long-term RES retention of WS₂-PEG and TiS₂-PEG. Our work suggests that MoS₂, among other TMDCs, may be particularly interesting for further biomedical applications owning to its low toxicity, capability of biodegradation, and rapid excretion.