4.8 Article

Localized disruption of redox homeostasis boosting ferroptosis of tumor by hydrogel delivery system

期刊

MATERIALS TODAY BIO
卷 12, 期 -, 页码 -

出版社

ELSEVIER
DOI: 10.1016/j.mtbio.2021.100154

关键词

Ferroptosis; Redox homeostasis; Glutathione peroxidase; Alkyl radicals; Hydrogel

资金

  1. Key Projects in Liaoning Province [2020JH2/10300046]

向作者/读者索取更多资源

Ferroptosis, targeting resistant tumor cells, is enhanced by localized injection of a trigger containing gambogic acid, AIPH, and Ink, along with laser irradiation to increase toxic lipid peroxides in tumor cells. This strategy disrupts intracellular redox homeostasis and boosts ferroptosis, showing promising efficacy in tumor suppression.
Ferroptosis has received ever-increasing attention due to its unparalleled mechanism in eliminating resistant tumor cells. Nevertheless, the accumulation of toxic lipid peroxides (LPOs) at the tumor site is limited by the level of lipid oxidation. Herein, by leveraging versatile sodium alginate (ALG) hydrogel, a localized ferroptosis trigger consisting of gambogic acid (GA), 2,2'-azobis [2-(2-imidazolin-2-yl) propane] dihydrochloride (AIPH), and Ink (a photothermal agent), was constructed via simple intratumor injection. Upon 1064 nm laser irradiation, the stored AIPH rapidly decomposed into alkyl radicals (R center dot), which aggravated LPOs in tumor cells. Meanwhile, GA could inhibit heat shock protein 90 (HSP90) to reduce the heat resistance of tumor cells, and forcefully consume glutathione (GSH) to weaken the antioxidant capacity of cells. Systematic in vitro and in vivo experiments have demonstrated that synchronous consumption of GSH and increased reactive oxygen species (ROS) facilitated reduced expression of glutathione peroxidase 4 (GPX4), which further contributed to disruption of intracellular redox homeostasis and ultimately boosted ferroptosis. This all-in-one strategy has a highly effective tumor suppression effect by depleting and generating fatal active compounds at tumor sites, which would pave a new route for the controllable, accurate, and coordinated tumor treatments.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.8
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据