活性氧
氧化还原
肿瘤微环境
谷胱甘肽
平衡
化学
生物物理学
激进的
NADPH氧化酶
细胞生物学
癌症研究
生物化学
酶
生物
肿瘤细胞
无机化学
作者
Zhongwen Yuan,Xinxin Liu,Jiabao Ling,Guanning Huang,Jia‐Run Huang,Xueqiong Zhu,Lizhen He,Tianfeng Chen
出处
期刊:Biomaterials
[Elsevier]
日期:2022-06-07
卷期号:287: 121620-121620
被引量:43
标识
DOI:10.1016/j.biomaterials.2022.121620
摘要
Disrupting redox homeostasis in the tumor microenvironment (TME), like excessive H2O2, glutathione (GSH) and weak acidity, has been proved as an effective tumor therapeutic strategy. Herein, we constructed a TME-responsive nanozyme, DOX@HMSN/Mn3O4(R), with reversible Mn3+/Mn2+ transition in situ triggered by TME to perturb the intrinsic redox homeostasis and catalyze reactive oxygen species (ROS) overproduction. In addition, this nanozyme could react with excess GSH in TME to produce GSSG, resulting in the consumption of reducing agents to suppress ROS clearance. Density functional theory calculations further confirmed that the nanozyme mainly exhibited the oxidase-like activity to catalyze the formation of hydroxyl radicals from O2, thus strengthening the oxidation environment in the TME. Combined with radiotherapy, the high-energy X-ray could excite the outer-layer electrons in the nanozyme, forming photoelectrons that participate in the oxidase-like enzymatic reaction, thus intensifying ROS accumulation and amplifying the radio-/chemotherapeutic efficacy.
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