Ultra-small MoS₂ nanodots with rapid body clearance for photothermal cancer therapy

The clinical translation of many inorganic nanomaterials is severely hampered by toxicity issues because of the long-term retention of these nanomaterials in the body. In this study, we developed a bio-clearable theranostic agent based on ultra-small MoS₂ nanodots, which were synthesized by a facile bottom-up approach through one-step solvothermal decomposition of ammonium tetrathiomolybdate. After modification by glutathione (GSH), the obtained MoS₂-GSH nanodots exhibited sub-10-nm hydrodynamic diameters without aggregation in various physiological buffers. Without showing appreciable in vitro toxicity, such MoS₂-GSH nanodots with strong near-infrared (NIR) absorbance could induce remarkable photothermal ablation of cancer cells. Upon intravenous (i.v.) injection, efficient tumor accumulation of MoS₂-GSH nanodots was observed by photoacoustic imaging, and further confirmed by analysis of the biodistribution of Mo. Notably, the MoS₂-GSH nanodots, in contrast to conventional MoS₂ nanoflakes with larger sizes, showed rather efficient body clearance via urine, where the majority of the injected dose was cleared within just seven days. Photothermal ablation of tumors on mice was then realized with the MoS₂-GSH nanodots, achieving excellent therapeutic efficacy. This study presents a new type of ultra-small nanoparticle with efficient tumor homing/treatment abilities, as well as rapid body clearance behavior, making it promising for cancer theranostics without long-term toxicity concerns.