Stimuli-Responsive Manganese Single-Atom Nanozyme for Tumor Therapy via Integrated Cascade Reactions

The single-atom enzyme (SAE) is a novel type of nanozyme that exhibits extraordinary catalytic activity. Here, we constructed a PEGylated manganese-based SAE (Mn/PSAE) by coordination of single-atom manganese to nitrogen atoms in hollow zeolitic imidazolate frameworks. Mn/PSAE catalyzes the conversion of cellular H₂ O₂ to ^. OH through a Fenton-like reaction; it also promotes the decomposition of H₂ O₂ to O₂ and continuously catalyzes the conversion of O₂ to cytotoxic ^. O₂^- via oxidase-like activity. The catalytic activity of Mn/PSAE is more pronounced in the weak acidic tumor environment; therefore, these cascade reactions enable the sufficient generation of reactive oxygen species (ROS) and effectively kill tumor cells. The prominent photothermal conversion property of the amorphous carbon can be utilized for photothermal therapy. Hence, Mn/PSAE exhibits significant therapeutic efficacy through tumor microenvironment stimulated generation of multiple ROS and photothermal activity.