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Application of glutathione depletion in cancer therapy: Enhanced ROS-based therapy, ferroptosis, and chemotherapy
Biomaterials ( IF 14.0 ) Pub Date : 2021-08-30 , DOI: 10.1016/j.biomaterials.2021.121110
Boyi Niu 1 , Kaixin Liao 1 , Yixian Zhou 1 , Ting Wen 1 , Guilan Quan 2 , Xin Pan 1 , Chuanbin Wu 3
Affiliation  

Glutathione (GSH) is an important member of cellular antioxidative system. In cancer cells, a high level of GSH is indispensable to scavenge excessive reactive oxygen species (ROS) and detoxify xenobiotics, which make it a potential target for cancer therapy. Plenty of studies have shown that loss of intracellular GSH makes cancer cells more susceptible to oxidative stress and chemotherapeutic agents. GSH depletion has been proved to improve the therapeutic efficacy of ROS-based therapy (photodynamic therapy, sonodynamic therapy, and chemodynamic therapy), ferroptosis, and chemotherapy. In this review, various strategies for GSH depletion used in cancer therapy are comprehensively summarized and discussed. First, the functions of GSH in cancer cells are analyzed to elucidate the necessity of GSH depletion in cancer therapy. Then, the synthesis and metabolism of GSH are briefly introduced to bring up some crucial targets for GSH modulation. Finally, different approaches to GSH depletion in the literature are classified and discussed in detail according to their mechanisms. Particularly, functional materials with GSH-consuming ability based on nanotechnology are elaborated due to their unique advantages and potentials. This review presents the ingenious application of GSH-depleting strategy in cancer therapy for improving the outcomes of various therapeutic regimens, which may provide useful guidance for designing intelligent drug delivery system.



中文翻译:

谷胱甘肽耗竭在癌症治疗中的应用:基于活性氧的增强疗法、铁死亡和化疗

谷胱甘肽(GSH)是细胞抗氧化系统的重要成员。在癌细胞中,高水平的谷胱甘肽对于清除过量的活性氧 (ROS) 和解毒外源性物质是必不可少的,这使其成为癌症治疗的潜在目标。大量研究表明,细胞内谷胱甘肽的损失使癌细胞更容易受到氧化应激和化疗药物的影响。GSH 消耗已被证明可以提高基于 ROS 的疗法(光动力疗法、声动力疗法和化学动力学疗法)的治疗效果,铁死亡和化疗。在这篇综述中,全面总结和讨论了用于癌症治疗的各种谷胱甘肽消耗策略。首先,分析GSH在癌细胞中的功能以阐明在癌症治疗中消耗GSH的必要性。然后,简要介绍了 GSH 的合成和代谢,以提出 GSH 调节的一些关键目标。最后,根据其机制对文献中不同的 GSH 消耗方法进行了分类和详细讨论。特别是,基于纳米技术的具有GSH消耗能力的功能材料因其独特的优势和潜力而被精心设计。本综述介绍了谷胱甘肽消耗策略在癌症治疗中的巧妙应用,以改善各种治疗方案的结果,

更新日期:2021-09-02
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