Targeting GPX4-Dependent Ferroptosis via a Dihydroartemisinin-Conjugated Cross-Linked Lipoic Acid Nanodrug for Endometrial Carcinoma Therapy

IF 3.9 2区 化学 Q1 BIOCHEMICAL RESEARCH METHODS
Qi Cao, Xiao Wu, Juan Tan, Hanying Xu, Ying Zhang, Yang Hu, Yuxi Chen, Shiyong Zhang and Tian Tang*, 
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引用次数: 0

Abstract

Endometrial cancer (EC) is a significant global cause of cancer-related mortality. Chemoresistance is a major challenge in treating advanced or recurrent EC, necessitating the search for new anti-EC drugs. Dihydroartemisinin (DHA)-induced ferroptosis shows promise as a therapy for EC, but its poor solubility and insufficient antitumor potency hinder its clinical use. A novel nanodrug delivery system, DHA@cLAVs, was developed using cross-linked lipoic acid to enhance DHA solubility and antitumor efficacy. Benefiting from the pro-oxidant effects of lipoic acid on tumor cells and its improved water solubility, DHA@cLAVs outperformed DHA alone, showing promising ferroptosis-based antitumor effects via the c-jun/c-fos-GPX4 pathway in both in vitro and in vivo experiments, offering promising prospects for endometrial carcinoma treatment.

Abstract Image

通过双氢青蒿素偶联硫辛酸纳米药物靶向gpx4依赖性铁下垂治疗子宫内膜癌。
子宫内膜癌(EC)是全球癌症相关死亡的重要原因。化疗耐药是治疗晚期或复发性EC的主要挑战,需要寻找新的抗EC药物。双氢青蒿素(DHA)诱导的铁下垂是一种治疗EC的有效方法,但其溶解性差和抗肿瘤能力不足阻碍了其临床应用。利用交联硫辛酸开发了一种新型纳米药物递送系统DHA@cLAVs,以提高DHA的溶解度和抗肿瘤功效。得益于硫辛酸对肿瘤细胞的促氧化作用及其改善的水溶性,DHA@cLAVs在体外和体内实验中均优于单独的DHA,通过c-jun/c-fos-GPX4通路显示出良好的基于铁中毒的抗肿瘤作用,为子宫内膜癌的治疗提供了广阔的前景。
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来源期刊
Bioconjugate Chemistry
Bioconjugate Chemistry 生物-化学综合
CiteScore
9.00
自引率
2.10%
发文量
236
审稿时长
1.4 months
期刊介绍: Bioconjugate Chemistry invites original contributions on all research at the interface between man-made and biological materials. The mission of the journal is to communicate to advances in fields including therapeutic delivery, imaging, bionanotechnology, and synthetic biology. Bioconjugate Chemistry is intended to provide a forum for presentation of research relevant to all aspects of bioconjugates, including the preparation, properties and applications of biomolecular conjugates.
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