Curved Carbon-Supported Dual-Atom Nanozyme with Ascorbic Acid Oxidase Activity for Cascade Tumor Catalytic Therapy

The catalytic activity of single-atom nanozymes is highly influenced by the local electronic structure of the metal active centers. While existing regulatory strategies predominantly focus on modulating the adjacent coordinating atoms and coordination numbers, the impact of the surface curvature of the support on the localized electronic structure and bonding environment of single-atom active centers remains underexplored in nanozymes. Here, we have successfully anchored Fe-Cr dual single-atom sites onto the highly curved surface of a N-doped carbon support (denoted as C-Fe1Cr1NC). This resulting nanozyme exhibits elevated ascorbate oxidase- (AO-), peroxidase- (POD-), and glutathione oxidase- (GSHOx-)-like activities. In tumor therapy, C-Fe1Cr1NC leverages its exceptional AO-like activity to efficiently oxidize exogenous ascorbic acid, overcoming kinetic limitations in the tumor microenvironment while enabling the in situ generation of H2O2. This self-supplied H2O2 subsequently fuels its POD-like activity to generate reactive oxygen species, forming an efficient catalytic cascade that induces lipid peroxidation while concurrently depleting glutathione (GSH), thereby achieving potent tumoricidal effects. This work advances the understanding of metal active center construction on highly curved surfaces within carbon support materials, facilitating the development of highly effective nanozyme-based therapeutics.