Tumor Microenvironment-Triggered MoS2@GA-Fe Nanoreactor: A Self-Rolling Enhanced Chemodynamic Therapy and Hydrogen Sulfide Treatment for Hepatocellular Carcinoma

Abstract We report the preparation of gallic acid (GA)-modified MoS2 nanosheets (MoS2@GA) with high Fe(III) loading. The MoS2@GA-Fe can function as a “Fenton Nanoreactor” in the tumor microenvironment (TME), in which GA-Fe(III) can be reduced to GA-Fe(II) by glutathione (GSH) and amounts of reactive hydroxyl radicals (•OH) are generated during the Fenton reaction. Notably, the MoS2 degrades into small fragments during the process, and more Mo(IV) reaction sites are exposed on the surface, resulting in a “snowball effect” and enhanced •OH production. Furthermore, unsaturated S atoms can capture protons in the TME and form hydrogen sulfide (H2S). We combined the photoacoustic imaging and magnetic resonance imaging contrast properties of MoS2@GA-Fe and constructed an imaging-guided chemodynamic treatment, featuring excellent antitumor efficiency and biosafety. The TME-responsive “Fenton Nanoreactor” provides a promising strategy with enhanced translational potency for tumor therapy.