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用于癌症治疗的线粒体靶向化学动力疗法纳米药物

Mitochondria-Targeting Chemodynamic Therapy Nanodrugs for Cancer Treatment.

作者信息

Chen Qiaohui, Li Niansheng, Wang Xiaoyuan, Yang Yuqi, Xiang Yuting, Long Xingyu, Zhang Jinping, Huang Jia, Chen Li, Huang Qiong

机构信息

Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, China.

Hunan Provincial Key Laboratory of Cardiovascular Research, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, China.

出版信息

Front Pharmacol. 2022 Jan 10;13:847048. doi: 10.3389/fphar.2022.847048. eCollection 2022.

Abstract

Mitochondria, as one of the most critical subcellular organelles of cancer cells, are very vulnerable and often on the verge of oxidative stress. The classic chemodynamic therapy (CDT) directly employs endogenous chemical energy to trigger reactive oxygen species (ROS) burst and destroy tumor cells. However, the effectiveness of CDT is restricted by the limited diffusion distance and short half-life of ROS. From this perspective, the treatment method (mitochondria-targeting chemodynamic therapy nanodrugs, M-CDT nanodrugs) that can generate high levels of ROS at the mitochondrial site is extremely efficient and promising for cancer treatment. Currently, many emerging M-CDT nanodrugs have been demonstrated excellent spatial specificity and anti-cancer efficacy. In this minireview, we review various proof-of-concept researches based on different M-CDT nanodrugs designs to overcome the limits of the efficacy of CDT, mainly divided into four strategies: supplying HO, non-HO dependent CDT, eliminating GSH and enhancing by hyperthermia therapy (HT). These well-designed M-CDT nanodrugs greatly increase the efficacy of CDT. Finally, the progress and potential of M-CDT nanodrugs are discussed, as well as their limitations and opportunities.

摘要

线粒体作为癌细胞中最关键的亚细胞器之一,非常脆弱,常常处于氧化应激的边缘。经典的化学动力疗法(CDT)直接利用内源性化学能触发活性氧(ROS)爆发并破坏肿瘤细胞。然而,CDT的有效性受到ROS有限的扩散距离和短半衰期的限制。从这个角度来看,能够在线粒体部位产生高水平ROS的治疗方法(线粒体靶向化学动力疗法纳米药物,M-CDT纳米药物)对于癌症治疗极具效率和前景。目前,许多新兴的M-CDT纳米药物已展现出出色的空间特异性和抗癌疗效。在这篇综述中,我们回顾了基于不同M-CDT纳米药物设计的各种概念验证研究,以克服CDT疗效的局限性,主要分为四种策略:提供羟基自由基(·OH)、非·OH依赖的CDT、消除谷胱甘肽(GSH)以及通过热疗(HT)增强疗效。这些精心设计的M-CDT纳米药物极大地提高了CDT的疗效。最后,讨论了M-CDT纳米药物的进展和潜力,以及它们的局限性和机遇。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0298/8866723/309ed8aefac6/fphar-13-847048-g001.jpg

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