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

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

Authors :
Jun Sun
Xiao Kuang
Zhonggui He
Shiyi Zuo
Jinbo Li
Shujun Wang
Yinxian Yang
Bingjun Sun
Linxiao Li
Source :
Asian Journal of Pharmaceutical Sciences, Asian Journal of Pharmaceutical Sciences, Vol 16, Iss 6, Pp 784-793 (2021)
Publication Year :
2021
Publisher :
Shenyang Pharmaceutical University, 2021.

Abstract

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.<br />Graphical abstract Image, graphical abstract

Details

Language :
English
ISSN :
2221285X and 18180876
Volume :
16
Issue :
6
Database :
OpenAIRE
Journal :
Asian Journal of Pharmaceutical Sciences
Accession number :
edsair.doi.dedup.....1e50feeb0e6dd65c84875d92bccd6c5a