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.