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
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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