A GPX4-targeted photosensitizer to reverse hypoxia-induced inhibition of ferroptosis for non-small cell lung cancer therapy,Chemical Science

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A GPX4-targeted photosensitizer to reverse hypoxia-induced inhibition of ferroptosis for non-small cell lung cancer therapy
Chemical Science ( IF 7.6 ) Pub Date : 2023-08-03 , DOI: 10.1039/d3sc01597a
Qiao Hu ₁ , Wanjie Zhu ₁ , Jianjun Du _{1,

2} , Haoying Ge ₁ , Jiazhu Zheng ₁ , Saran Long _{1,

2} , Jiangli Fan _{1,

2} , Xiaojun Peng ₁

Affiliation

Ferroptosis therapy is gradually becoming a new strategy for the treatment of non-small cell lung cancer (NSCLC) because of its active iron metabolism. Because the hypoxic microenvironment in NSCLC inhibits ferroptosis heavily, the therapeutic effect of some ferroptosis inducers is severely limited. To address this issue, this work describes a promising photosensitizer ENBS-ML210 and its application against hypoxia of NSCLC treatment based on type I photodynamic therapy and glutathione peroxidase 4 (GPX4)-targeted ferroptosis. ENBS-ML210 can promote lipid peroxidation and reduce GPX4 expression by generating superoxide anion radicals under 660 nm light irradiation, which reverses the hypoxia-induced resistance of ferroptosis and effectively kills H1299 tumor cells. Finally, the excellent synergistic antitumor effects are confirmed both in vitro and in vivo. We firmly believe that this method will provide a new direction for the clinical treatment of NSCLC in the future.

中文翻译：

一种 GPX4 靶向光敏剂可逆转缺氧诱导的铁死亡抑制，用于非小细胞肺癌治疗

铁死亡疗法因其活跃的铁代谢而逐渐成为治疗非小细胞肺癌（NSCLC）的新策略。由于NSCLC中的缺氧微环境严重抑制铁死亡，一些铁死亡诱导剂的治疗效果受到严重限制。为了解决这个问题，这项工作描述了一种有前途的光敏剂ENBS-ML210及其在基于 I 型光动力疗法和谷胱甘肽过氧化物酶 4 (GPX4) 靶向铁死亡的 NSCLC 治疗缺氧中的应用。ENBS-ML210在660 nm光照射下可通过产生超氧阴离子自由基促进脂质过氧化并降低GPX4表达，逆转缺氧诱导的铁死亡抵抗，有效杀伤H1299肿瘤细胞。最后，在体外和体内均证实了其优异的协同抗肿瘤作用。我们坚信该方法将为未来NSCLC的临床治疗提供新的方向。

更新日期：2023-08-03

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