Iron-doxorubicin prodrug loaded liposome nanogenerator programs multimodal ferroptosis for efficient cancer therapy

Asian Journal of Pharmaceutical Sciences

Shujun Wang¹  Jin Sun¹  Yinxian Yang²  Zhonggui He²  Bingjun Sun³  Jinbo Li³  Xiao Kuang³  Shiyi Zuo³  Linxiao Li³ 

[1] Corresponding authors.;Department of Pharmaceutics, College of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China;Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China;

关键词: Ferroptosis;    Iron;    Liposome;    Redox;    Prodrug;   

DOI  :  

来源: DOAJ

【 摘 要 】

Ferroptosis is a new mode of cell death, which can be induced by Fenton reaction-mediated lipid peroxidation. However, the insufficient H2O2 and high GSH in tumor cells restrict the efficiency of Fenton reaction-dependent ferroptosis. Herein, a self-supplying lipid peroxide nanoreactor was developed to co-delivery of doxorubicin (DOX), iron and unsaturated lipid for efficient ferroptosis. By leveraging the coordination effect between DOX and Fe3+, trisulfide bond-bridged DOX dimeric prodrug was actively loaded into the core of the unsaturated lipids-rich liposome via iron ion gradient method. First, Fe3+could react with the overexpressed GSH in tumor cells, inducing the GSH depletion and Fe2+generation. Second, the cleavage of trisulfide bond could also consume GSH, and the released DOX induces the generation of H2O2, which would react with the generated Fe2+in step one to induce efficient Fenton reaction-dependent ferroptosis. Third, the formed Fe3+/Fe2+ couple could directly catalyze peroxidation of unsaturated lipids to boost Fenton reaction-independent ferroptosis. This iron-prodrug liposome nanoreactor precisely programs multimodal ferroptosis by integrating GSH depletion, ROS generation and lipid peroxidation, providing new sights for efficient cancer therapy.

【 授权许可】

Unknown