外体
三阴性乳腺癌
微泡
乳腺癌
癌症研究
医学
癌细胞
化学
癌症
程序性细胞死亡
内科学
细胞生物学
生物
细胞凋亡
基因
生物化学
小RNA
作者
Mengyu Yu,Chengcheng Gai,Zihaoran Li,Dejun Ding,Jie Zheng,Weifen Zhang,Shijun Lv,Wentong Li
出处
期刊:Cancer Science
[Wiley]
日期:2019-10-01
卷期号:110 (10): 3173-3182
被引量:209
摘要
Abstract Ferroptosis is an iron‐dependent, lipid peroxide‐driven cell death caused by inhibition of the cystine/glutamate transporter, which is of importance for the survival of triple‐negative breast cancer ( TNBC ) cells. Erastin is a low molecular weight chemotherapy drug that induces ferroptosis; however, poor water solubility and renal toxicity have limited its application. Exosomes, as drug delivery vehicles with low immunogenicity, high biocompatibility and high efficiency, have attracted increasing attention in recent years. Herein, we developed a formulation of erastin‐loaded exosomes labeled with folate ( FA ) to form FA ‐vectorized exosomes loaded with erastin (erastin@FA‐exo) to target TNBC cells with overexpression of FA receptors. The characterization, drug release, internalization and anti–tumor effect in vitro of erastin@ FA ‐exo were determined. Erastin@FA‐exo could increase the uptake efficiency of erastin into MDA ‐ MB ‐231 cells; compared with erastin@exo and free erastin, erastin@ FA ‐exo has a better inhibitory effect on the proliferation and migration of MDA ‐ MB ‐231 cells. Furthermore, erastin@ FA ‐exo promoted ferroptosis with intracellular depletion of glutathione and reactive oxygen species overgeneration. Western blot analyses revealed that erastin@ FA ‐exo suppressed expression of glutathione peroxidase 4 ( GPX 4) and upregulated expression of cysteine dioxygenase ( CDO 1). We conclude that targeting and biocompatibility of exosome‐based erastin preparations provide an innovative and powerful delivery platform for anti–cancer therapy.
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