Nanocatalytic Theranostics with Glutathione Depletion and Enhanced Reactive Oxygen Species Generation for Efficient Cancer Therapy

• Published in: Advanced materials (Weinheim) Vol. 33; no. 7; pp. e2006892 - n/a
• Main Authors: Fu, Lian‐Hua, Wan, Yilin, Qi, Chao, He, Jin, Li, Chunying, Yang, Chen, Xu, Han, Lin, Jing, Huang, Peng
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01-02-2021
• Subjects: Biocompatibility; Biodegradability; Calcium phosphates; Cancer; Cancer therapies; Copper; Depletion; Doxorubicin; Glucose oxidase; Glutathione; GSH depletion; Hydrogen peroxide; Hydroxyl radicals; Materials science; Nanoparticles; Polyethylene glycol; Redox reactions; self‐supply H2O2; Side effects; synergistic therapy; Tumors; cancer; synergistic therapy; GSH depletion; self-supply H2O2; glucose oxidase
• ISSN: 0935-9648; 1521-4095
• DOI: 10.1002/adma.202006892

Chemodynamic therapy (CDT) is an emerging therapy method that kills cancer cells by converting intracellular hydrogen peroxide (H2O2) into highly toxic hydroxyl radicals (•OH). To overcome the current limitations of the insufficient endogenous H2O2 and the high concentration of glutathione (GSH) in tumor cells, an intelligent nanocatalytic theranostics (denoted as PGC‐DOX) that possesses both H2O2 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 H2O2, which not only starves the tumor cells, but also supplies H2O2 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 H2O2 to generate •OH by a Cu+‐mediated Fenton‐like reaction, resulting in enhanced CDT efficacy. The integration of GOx‐mediated starvation therapy, H2O2 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.
A fully biodegradable and biocompatible nanotheranostic (denoted as PGC‐DOX) is constructed by an in situ biomineralization method using poly(ethylene glycol)‐modified glucose oxidase (GOx) as a template. The integration of GOx‐mediated starvation therapy, H2O2 self‐supplying and glutathione‐eliminating enhanced chemodynamic therapy, and DOX‐induced chemotherapy, means that the prepared PGC‐DOX is effective for tumor growth inhibition with minimal side effects in vivo.