GPX4
谷胱甘肽
化学
细胞内
胶束
PEG比率
细胞凋亡
生物化学
麦芽糖
程序性细胞死亡
癌细胞
细胞生物学
生物
酶
癌症
水溶液
经济
物理化学
财务
遗传学
谷胱甘肽过氧化物酶
作者
Wenhua Li,Xiaoying Li,Xu Cheng,Wenyuan Zhang,Gong Chen,Chuya Gao,Haisheng Peng,Bo Yang,Shu‐Kun Tang,Haiquan Tao
标识
DOI:10.1080/1061186x.2021.1953511
摘要
Ferroptosis is a regulated cell death pathway which depends on iron. Ferroptosis can be induced by limiting intracellular glutathione (GSH) synthesis, or inhibiting the activity of GPX4, or increasing intracellular accumulation of PE-AA-OOH, all of which involve NADPH. Therefore, NADPH depletion, excessive PE-AA-OOH, and GPX4 deficiency are generally considered to be the main characteristics of ferroptosis. In this research, the novel self-assembly nanomicelles modified by maltose ligand (Malt-PEG-Abz@RSL3) with superior nano characteristics were designed and fabricated. Malt-PEG-Abz@RSL3 micelles achieved active targeted drug delivery due to the high expression of glucose transporter (GLUT) and high uptake by HepG2 cells. Maltose-polyethylene glycol broke to release RSL3 for inhibiting GPX4 activity when Malt-PEG-Abz@RSL3 micelles entered the cells. Meanwhile, key coenzyme NADPH that participated in synthesis of GSH and Trx(SH)2 was depleted by azobenzene moiety, resulting in decreasing GSH and Trx(SH)2, which dually induced ferroptosis in tumour cells and promoted cell apoptosis.
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