Tumor microenvironment responsive and nanozyme‐catalyzed photodynamic therapy via lysosome‐localized copper‐doped carbon dots

Abstract The tumor microenvironment (TME), characterized by hypoxia, glutathione (GSH) overexpression and elevated H 2 O 2 , limits photodynamic therapy (PDT) but also offers novel therapeutic tools for antitumor strategies. Herein, lysosome‐localized copper‐doped carbon dots (Cu‐MLCDs) were developed as a TME‐responsive nanozyme platform for fluorescence‐guided, self‐amplified PDT. MLCDs were synthesized by one‐pot hydrothermal method of methylene blue and levofloxacin, and Cu‐MLCDs were subsequently obtained through Cu 2+ doping. Cu doping markedly quenched basal fluorescence, whereas GSH/H 2 O 2 ‐rich TME conditions reactivated deep‐red emission, thereby enabling bright fluorescence imaging. Under red laser irradiation (660 nm), Cu‐MLCDs generated singlet oxygen ( 1 O 2 ) and hydroxyl radicals (·OH) for PDT. Concurrently, Cu‐MLCDs exhibited GSH peroxidase‐like activity to deplete intratumoral GSH, peroxidase‐like activity to convert H 2 O 2 into highly toxic ·OH, and catalase‐like activity to relieve hypoxia by generating O 2 . These reactions remodeled the TME, weakened antioxidant defense and amplified oxidative stress. Lysosomal accumulation further concentrated reactive oxygen species generation at vulnerable subcellular sites, inducing lipid peroxidation, membrane damage, mitochondrial dysfunction and cancer cell death. This study establishes a lysosome‐localized, TME‐responsive CDs nanozyme platform that integrates TME‐activated fluorescence imaging and enzyme‐like catalysis‐driven self‐augmented PDT.