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

作　　者：Yinxian Yang Shiyi Zuo Linxiao Li Xiao Kuang Jinbo Li Bingjun Sun Shujun Wang Zhonggui He Jin Sun 

机构地区：[1]Department of Pharmaceutics,College of Pharmacy,Shenyang Pharmaceutical University,Shenyang 110016,China [2]Department of Pharmaceutics,Wuya College of Innovation,Shenyang Pharmaceutical University,Shenyang 110016,China

出　　处：《Asian Journal of Pharmaceutical Sciences》2021年第6期784-793,共10页亚洲药物制剂科学（英文）

基　　金：supported by the National Natural Science Foundation of China(no.81872816);the Liaoning Revitalization Talents Program(no.XLYC180801);China Postdoctoral Innovative Talents Support Program(no.BX20190219);China Postdoctoral Science Foundation(no.2019M661134).

摘　　要：Ferroptosis is a new mode of cell death,which can be induced by Fenton reactionmediated 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.

关 键 词：Ferroptosis Iron LIPOSOME Redox PRODRUG 

分 类 号：R730.5[医药卫生—肿瘤]