Scheme 1
Schematic illustration of (A) the preparation of CuMnOx−V@Oxa@SP NFs and (B) CuMnOx−V@Oxa@SP NFs exhibit multiple enzyme-mimicking activities, delivering the chemotherapeutic drug oxaliplatin while catalyzing the production of various ROS, including ·OH, ·O₂⁻, and ¹O₂, to induce a ROS storm that synergistically promotes apoptosis. Additionally, they act as nanoNAD oxidases, rapidly and irreversibly depleting NAD+ and NADH, reducing ATP production, and disrupting the electron transport chain, leading to mitochondrial dysfunction. Furthermore, the NFs downregulate GSTP1, a key detoxification enzyme in chemoresistant tumors, enhancing oxaliplatin accumulation by inhibiting its metabolism. This multiple mechanism synergistically overcomes drug resistance and enhances antitumor efficacy