GPX4
材料科学
纳米载体
纳米技术
细胞凋亡
谷胱甘肽
微泡
程序性细胞死亡
氧化应激
活性氧
化学
生物化学
癌症研究
谷胱甘肽过氧化物酶
酶
生物
药物输送
小RNA
基因
作者
Wenli Feng,Wanrui Shi,Ze Wang,Yanqi Cui,Xinxin Shao,Shuwei Liu,Rong Li,Fangmeng Liu,Hao Zhang
标识
DOI:10.1021/acsami.2c11130
摘要
Ferroptosis has been considered as a promising pathway to overcome apoptosis-induced tumor chemoresistance. However, the antitumor efficacy of ferroptosis-inducing agents is still limited because of the complexity and diversity of tumor microenvironments. Herein, we demonstrate a triple ferroptosis amplification strategy for tumor therapy by associating iron-based nanocarriers, ferroptosis molecular drugs, and H2O2-producing enzymes. Fe(III)-Shikonin (FeShik) metal-polyphenol-coordinated networks are employed to load a ferroptosis inducer of sorafenib (SRF) inside and glucose oxidase (GOx) outside, thus producing SRF@FeShik-GOx supramolecular nanomedicines (SNs). After delivering into glutathione (GSH)-overexpressed tumor cells, FeShik will disassemble and release Fe2+ to induce cell death via ferroptosis. At the same time, GOx executes its catalytic activity to produce an acid environment and plenty of H2O2 for stimulating •OH generation via the Fenton reaction. Moreover, SRF will suppress the biosynthesis of GSH by inhibiting system Xc-, further deactivating the enzymatic activity of glutathione peroxidase 4 (GPX4). Up-regulation of the oxidative stress level and down-regulation of GPX4 expression can dramatically accelerate the accumulation of lethal lipid peroxides, leading to ferroptosis amplification of tumor cells. The current strategy that utilizes ferroptosis-inducing agents as both nanocarriers and cargoes provides a pathway to enhance the efficacy of ferroptosis-based tumor therapy.
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