Atomically dispersed bimetallic active sites as H2O2 self-supplied nanozyme for effective chemodynamic therapy, chemotherapy and starvation therapy

Tumor microenvironment (TME)-responsive chemodynamic therapy (CDT) is severely hindered by insufficient intracellular H₂O₂ level that seriously deteriorates antitumor efficacy, albeit with its extensively experimental and theoretical research. Herein, we designed atomically dispersed FeCo dual active sites anchored in porous carbon polyhedra (termed FeCo/PCP), followed by loading with glucose oxidase (GOx) and anticancer doxorubicin (DOX), named FeCo/PCP-GOx-DOX, which converted glucose into toxic hydroxyl radicals. The loaded GOx can either decompose glucose to self-supply H₂O₂ or provide fewer nutrients to feed the tumor cells. The as-prepared nanozyme exhibited the enhanced in vitro cytotoxicity at high glucose by contrast with those at less or even free of glucose, suggesting sufficient accumulation of H₂O₂ and continual transformation to OH for CDT. Besides, the FeCo/PCP-GOx-DOX can subtly integrate starvation therapy, the FeCo/PCP-initiated CDT, and DOX-inducible chemotherapy (CT), greatly enhancing the therapeutic efficacy than each monotherapy.