GPX4
活性氧
雷公藤甲素
谷胱甘肽
化学
双重角色
胶质母细胞瘤
癌症研究
脂质过氧化
过氧化脂质
谷胱甘肽过氧化物酶
抗氧化剂
生物化学
医学
酶
细胞凋亡
组合化学
作者
Hongshuai Wu,Pingping Cao,Haiyang Wang,Wenhong Wang,Hangyang Yu,Chaoqun You,Tianqi Shen,Suisui Yang,Ziyi Hu,Tingting Zhou,Jing Wang,Qianghu Wang,Qian Xu,Junxia Zhang,Xiuxing Wang,Yuandong Cao,Like Ning,Fan Lin
出处
期刊:Small
[Wiley]
日期:2024-10-07
标识
DOI:10.1002/smll.202406036
摘要
Abstract Glioblastoma (GBM) recurrence leads to high mortality, which remains a major concern in clinical therapy. Herein, an injectable triptolide (TP)‐preloaded hydrogel (TP@DNH) accompanied by a postoperative injection strategy is developed to prevent the recurrence of GBM. With a potential inhibitor of the NRF2/SLC7A11/GPX4 axis, it is demonstrated that TP can deactivate glutathione peroxidase 4 (GPX4) from the source of glutathione (GSH) biosynthesis, thereby activating ferroptosis in GBM cells by blocking the neutralization of intracellular lipid peroxide (LPO). Based on acid‐sensitive Fe 3+ /tannic acid (TA) metal‐phenolic networks (MPNs), the TP@DNH hydrogel can induce the effective generation of reactive oxygen species (ROS) through Fe 3+ /TA‐mediated Fenton reaction and achieve controllable release of TP in resected GBM cavity. Due to ROS generation and GPX4 deactivation, postoperative injection of TP@DNH can achieve high‐level ferroptosis through dual‐pathway LPO accumulation, remarkably suppressing the growth of recurrent GBM and prolonging the overall survival in orthotopic GBM relapse mouse model. This work provides an alternative paradigm for regulating ferroptosis in the postoperative treatment of GBM.
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