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Nanocatalytic Theranostics with Glutathione Depletion and Enhanced Reactive Oxygen Species Generation for Efficient Cancer Therapy
Author(s) -
Fu LianHua,
Wan Yilin,
Qi Chao,
He Jin,
Li Chunying,
Yang Chen,
Xu Han,
Lin Jing,
Huang Peng
Publication year - 2021
Publication title -
advanced materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 10.707
H-Index - 527
eISSN - 1521-4095
pISSN - 0935-9648
DOI - 10.1002/adma.202006892
Subject(s) - glutathione , hydrogen peroxide , doxorubicin , glucose oxidase , reactive oxygen species , intracellular , ethylene glycol , radical , cancer cell , catalysis , materials science , combinatorial chemistry , chemistry , biophysics , biochemistry , cancer , chemotherapy , enzyme , organic chemistry , biology , genetics
Chemodynamic therapy (CDT) is an emerging therapy method that kills cancer cells by converting intracellular hydrogen peroxide (H 2 O 2 ) into highly toxic hydroxyl radicals ( • OH). To overcome the current limitations of the insufficient endogenous H 2 O 2 and the high concentration of glutathione (GSH) in tumor cells, an intelligent nanocatalytic theranostics (denoted as PGC‐DOX) that possesses both H 2 O 2 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 H 2 O 2 , which not only starves the tumor cells, but also supplies H 2 O 2 for subsequent Fenton‐like reaction. Meanwhile, the redox reaction between the released Cu 2+ ions and intracellular GSH will induce GSH depletion and reduce Cu 2+ to Fenton agent Cu + ions, and then trigger the H 2 O 2 to generate • OH by a Cu + ‐mediated Fenton‐like reaction, resulting in enhanced CDT efficacy. The integration of GOx‐mediated starvation therapy, H 2 O 2 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.