Abstract

Abstract Chemodynamic therapy (CDT) has garnered significant attention in the field of tumor therapy due to its ability to convert overexpressed hydrogen peroxide (H 2 O 2 ) in tumors into highly toxic hydroxyl radicals (•OH) through metal ion‐mediated catalysis. However, the effectiveness of CDT is hindered by low catalyst efficiency, insufficient intra‐tumor H 2 O 2 level, and excessive glutathione (GSH). In this study, a pH/GSH dual responsive bimetallic nanocatalytic system (CuFeMOF@GOx@Mem) is developed by modifying red blood cell membranes onto glucose oxidase (GOx)‐loaded Fe‐Cu bimetallic MOFs, enhancing the efficacy of CDT through a triple‐enhanced way by H 2 O 2 self‐supply, catalysts self‐cycling, and GSH self‐elimination. Upon accumulation in tumor tissues facilitated by the red blood cell membrane, the GOx initiates a reaction with glucose to generate H 2 O 2 and gluconic acid in situ. Subsequently, the reduced pH triggers the release of Fe 3+ and Cu 2+ from CuFeMOF@GOx@Mem, which is immediately turned into Fe 2+ and Cu + by GSH, activating the Fe 2+ ‐mediated Fenton reaction. More importantly, Cu + can also act as an accelerator of Fe 3+ /Fe 2+ conversion, meanwhile, the generated Cu 2+ can be further reduced to Cu + by GSH. Consequently, sustained accumulation of H 2 O 2 and Fe 2+ as well as sustained elimination of GSH are achieved simultaneously, providing a unique approach for improving the anti‐tumor ability of CDT.