Tumor microenvironment-triggered MoS2@GA-Fe nanoreactor: A self-rolling enhanced chemodynamic therapy and hydrogen sulfide treatment for hepatocellular carcinoma

We report the preparation of gallic acid (GA)-modified MoS 2 nanosheets (MoS 2 @GA) with high Fe(III) loading. The MoS 2 @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 MoS 2 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 (H 2 S). We combined the photoacoustic imaging and magnetic resonance imaging contrast properties of MoS 2 @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.