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Sorafenib-Loaded Copper Peroxide Nanoparticles with Redox Balance Disrupting Capacity for Enhanced Chemodynamic Therapy against Tumor Cells
Chen, Chunmei1; Tan, Yixin1; Xu, Ting1; Sun, Yihao1; Zhao, Sheng1; Ouyang, Yi1; Chen, Yan1; He, Liang1; Liu, Xiaohong2,3; Liu, Hui1
2022-09-26
摘要Chemodynamic therapy (CDT) is a promising hydroxyl radical (center dot OH)-mediated tumor therapeutic method with desirable tumor specificity and minimal side effects. However, the efficiency of CDT is restricted by the pH condition, insufficient H2O2 level, and overexpressed reductive glutathione (GSH), making it challenging to solve these problems simultaneously to improve the efficacy of CDT. Herein, a kind of polyvinylpyrro-lidone-stabilized, sorafenib-loaded copper peroxide (CuO2-PVP-SRF) nanoparticle (NPs) was designed and developed for enhanced CDT against tumor cells through the synergetic pH-independent Fenton-like, H2O2 self-supplying, and GSH depletion strategy. The prepared CuO2-PVP-SRF NPs can be uptaken by 4T1 cells to specifically release Cu2+, H2O2, and SRF under acidic conditions. The intracellular GSH can be depleted by SRF-induced system xc- dysfunction and Cu2+-participated redox reaction, causing the inactivation of GPX4 and generating Cu+. A great amount of center dot OH was produced in this reducing capacity-disrupted condition by the Cu+-mediated Fenton-like reaction, causing cell apoptosis and lipid hydroperoxide accumulation-induced ferroptosis. They display an excellent 4T1 cell killing outcome through the improved center dot OH production capacity. The CuO2-PVP-SRF NPs display elevated therapeutic efficiency of CDT and show good promise in further tumor treatment applications.
DOI10.1021/acs.langmuir.2c01938
发表期刊LANGMUIR
ISSN0743-7463
页码9
通讯作者Liu, Xiaohong(lxhsuda@163.com) ; Liu, Hui(liuhui2016@swu.edu.cn)
收录类别SCI
WOS记录号WOS:000862357500001
语种英语