Dual Glutathione Depletion Enhanced Enzyme Catalytic Activity for Hyperthermia Assisted Tumor Therapy on Semi-Metallic VSe2/Mn-CS

Semimetallic nanomaterials as photothermal agents for bioimaging and cancer therapy have attracted tremendous interest. However, the poor photothermal stability, low biocompatibility, and single component limit their therapeutic efficiency in cancer treatment. Here, manganese-doped VSe₂ semimetallic nanosheets were prepared and subsequently modified with chitosan (named VSe₂/Mn-CS NSs) for combined enzyme catalytic and photothermal therapy. VSe₂/Mn-CS NSs show high photothermal property with a photothermal conversion efficiency of 34.61% upon 808 nm near-infrared laser irradiation. In the tumor microenvironment, VSe₂/Mn-CS NSs can convert endogenous H₂O₂ into lethal hydroxyl radicals (?OH) to induce cancer cell apoptosis. The interaction between glutathione (GSH) and Se–Se bonds in VSe₂/Mn-CS NSs results in the depletion of GSH level, and the valence states transition of manganese ions is also beneficial for the GSH consumption. This dual depletion of GSH markedly enhances the peroxidase (POD) activity, leading to the high ?OH production and the improved therapeutic effect. What is more, the T₁-weighted magnetic resonance and photoacoustic imaging endow VSe₂/Mn-CS NSs with the ability to guide and track the treatment process. Our study provides a research strategy for the application of semimetallic nanomaterials in cancer diagnosis and treatment.