谷胱甘肽
线粒体
三阴性乳腺癌
活性氧
化学
癌细胞
GPX4
癌症研究
程序性细胞死亡
细胞生物学
谷胱甘肽过氧化物酶
细胞凋亡
癌症
生物化学
生物
乳腺癌
酶
遗传学
作者
Hongbo Gan,Xie Huang,Xi Luo,Jinlin Li,Banghui Mo,Lizhi Cheng,Qiuxia Shu,Zaizhi Du,Hong Tang,Wei Sun,Liting Wang,Shenglin Luo,Songtao Yu
标识
DOI:10.1002/adhm.202300220
摘要
Abstract Ferroptosis is a new type of iron‐dependent programmed cell death characterized by glutathione (GSH) depletion, selenoprotein glutathione peroxidase 4 (GPX4) inactivation, and lipid peroxides accumulation. Mitochondria, as the main source of intracellular energy supply and reactive oxygen species (ROS) generation, play a central role in oxidative phosphorylation and redox homeostasis. Therefore, targeting cancer‐cell mitochondria and attacking redox homeostasis is expected to induce robust ferroptosis‐mediated anticancer effects. In this work, a theranostic ferroptosis inducer ( IR780‐SPhF ), which can simultaneously achieve the imaging and therapy of triple‐negative breast cancer (TNBC) by targeting mitochondria is presented. It is developed from a mitochondria‐targeting small molecule ( IR780 ) with cancer‐preferential accumulation, enabling it to react with GSH by nucleophilic substitution, resulting in mitochondrial GSH depletion and redox imbalance. More interestingly, IR780‐SPhF exhibits GSH‐responsive near‐infrared fluorescence emission and photoacoustic imaging characteristics, further facilitating diagnosis and treatment with real‐time monitoring of TNBC with a highly elevated GSH level. Both in vitro and in vivo results demonstrate that IR780‐SPhF exhibits potent anticancer effect, which is significantly stronger than cyclophosphamide, a classic drug commonly recommended for TNBC patients in clinic. Hence, the reported mitochondria‐targeted ferroptosis inducer may represent a promising candidate and a prospective strategy for efficient cancer treatment.
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