一氧化氮
过氧化氢
谷胱甘肽
化学
氧化应激
激进的
羟基自由基
芬顿反应
癌症研究
药理学
生物化学
医学
有机化学
酶
作者
Weijiang Yu,Fan Jia,Junzhe Fu,Yonghang Chen,Yan Huang,Qiao Jin,Youxiang Wang,Jian Ji
出处
期刊:ACS Nano
[American Chemical Society]
日期:2023-08-11
卷期号:17 (16): 15713-15723
被引量:21
标识
DOI:10.1021/acsnano.3c02964
摘要
Chemodynamic therapy (CDT) has emerged as a promising strategy for cancer treatment. However, its effectiveness has been hindered by insufficient hydrogen peroxide (H2O2) and high reductive glutathione (GSH) within tumors, which are the two main reasons for the inefficiency of Fenton/Fenton-like reaction-based CDT. Herein, we present a H2O2 boost-GSH depletion strategy for enhanced CDT to fight against melanoma through a microneedle (MN)-based transcutaneous delivery method. The MN system is composed of dissolvable polyvinylpyrrolidone integrated with stimuli-responsive prodrugs. Under an intracellular acidic environment, the smart release of H2O2 boosting components is triggered, subsequently initiating nitric oxide (NO) release and enhancing the Fenton-like reaction in a cascade manner. The generation of hydroxyl radicals (•OH), along with the depletion of GSH by NO, amplifies the oxidative stress within tumor cells, promoting apoptosis and ferroptosis. The antitumor efficacy of the MN patch is validated in an A375 mouse melanoma model. This "H2O2 boost-GSH depletion-Fenton killing" strategy expands the options for superficial tumor treatment through MN-mediated enhanced CDT.
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