Chemodynamic therapy (CDT) is an emerging therapy method that kills cancer cells by converting intracellular hydrogen peroxide (H₂ O₂ ) into highly toxic hydroxyl radicals (^• OH). To overcome the current limitations of the insufficient endogenous H₂ O₂ and the high concentration of glutathione (GSH) in tumor cells, an intelligent nanocatalytic theranostics (denoted as PGC-DOX) that possesses both H₂ O₂ self-supply and GSH-elimination properties for efficient cancer therapy is presented. This nanoplatform is constructed by a facile one-step biomineralization method using poly(ethylene glycol)-modified glucose oxidase (GOx) as a template to form biodegradable copper-doped calcium phosphate nanoparticles, followed by the loading of doxorubicin (DOX). As an enzyme catalyst, GOx can effectively catalyze intracellular glucose to generate H₂ O₂ , which not only starves the tumor cells, but also supplies H₂ O₂ for subsequent Fenton-like reaction. Meanwhile, the redox reaction between the released Cu²⁺ ions and intracellular GSH will induce GSH depletion and reduce Cu²⁺ to Fenton agent Cu⁺ ions, and then trigger the H₂ O₂ to generate ^• OH by a Cu⁺ -mediated Fenton-like reaction, resulting in enhanced CDT efficacy. The integration of GOx-mediated starvation therapy, H₂ O₂ self-supply and GSH-elimination enhanced CDT, and DOX-induced chemotherapy, endow the PGC-DOX with effective tumor growth inhibition with minimal side effects in vivo.

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