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H 2 O 2 Self-Supplying and GSH-Depleting Nanocatalyst for Copper Metabolism-Based Synergistic Chemodynamic Therapy and Chemotherapy.

Zhaomin TangShuting JiangWanlan TangQian HeHuangzhao WeiChengyu JinShuai WangHui Zhang
Published in: Molecular pharmaceutics (2023)
Chemodynamic therapy (CDT) that involves the use of Fenton catalysts to convert endogenous hydrogen peroxide (H 2 O 2 ) to hydroxyl radicals (·OH) constitutes a promising strategy for cancer therapy; however, insufficient endogenous H 2 O 2 and glutathione (GSH) overexpression render its efficiency unsatisfactory. Herein, we present an intelligent nanocatalyst that comprises copper peroxide nanodots and DOX-loaded mesoporous silica nanoparticles (MSNs) (DOX@MSN@CuO 2 ) and can self-supply exogenous H 2 O 2 and respond to specific tumor microenvironments (TME). Following endocytosis into tumor cells, DOX@MSN@CuO 2 initially decomposes into Cu 2+ and exogenous H 2 O 2 in the weakly acidic TME. Subsequently, Cu 2+ reacts with high GSH concentrations, thereby inducing GSH depletion and reducing Cu 2+ to Cu + Next, the generated Cu + undergoes Fenton-like reactions with exogenous H 2 O 2 to accelerate toxic ·OH production, which exhibits a rapid reaction rate and is responsible for tumor cell apoptosis, thereby enhancing CDT. Furthermore, the successful delivery of DOX from the MSNs achieves chemotherapy and CDT integration. Thus, this excellent strategy can resolve the problem of insufficient CDT efficacy due to limited H 2 O 2 and GSH overexpression. Integrating H 2 O 2 self-supply and GSH deletion enhances CDT, and DOX-induced chemotherapy endows DOX@MSN@CuO 2 with effective tumor growth-inhibiting properties alongside minimal side effects in vivo.
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