A glutathione-responsive sulfur dioxide polymer prodrug selectively induces ferroptosis in gastric cancer therapy

被引：22
作者：
Xia, Mingjie [1 ,2 ]
Guo, Zhihui [3 ]
Liu, Xinming [3 ]
Wang, Yang [1 ]
Xiao, Chunsheng [3 ]
机构：
[1] Northeast Normal Univ, Key Lab Mol Epigenet, Minist Educ, Changchun 130024, Peoples R China
[2] First Hosp Jilin Univ, Dept Gastrointestinal Surg, Changchun 130021, Peoples R China
[3] Chinese Acad Sci, Changchun Inst Appl Chem, Key Lab Polymer Ecomat, Changchun 130022, Peoples R China
来源：
BIOMATERIALS SCIENCE | 2022年 / 10卷 / 15期
基金：
中国国家自然科学基金;
关键词：
CELL-DEATH; SO2; RELEASE; GAS; ROS;
D O I：
10.1039/d2bm00678b
中图分类号：
TB3 [工程材料学]; R318.08 [生物材料学];
学科分类号：
0805 ; 080501 ; 080502 ;
摘要：
Nanoparticle-induced ferroptosis has been proven to be an appealing strategy in cancer treatment. Previously, we reported the synthesis of an amphiphilic polymer prodrug of SO2, mPEG-PLG(DNs), which could self-assemble to formulate nanoparticles (NP-DNs) and trigger cancer cell death by GSH consumption and SO2 release. In the current study, the potential mechanism of NP-DNs-induced cell death was further investigated. We demonstrated that NP-DNs exhibited efficient antitumor activity against gastric cancer via ferroptosis. NP-DNs could selectively accelerate lipid peroxidation through GSH depletion and SO2 generation in gastric cancer cells. In addition, the NP-DNs-induced GPX4 reduction played a collaborative role in ferroptosis. Concurrently, in vivo evaluations revealed that NP-DNs not only exhibited excellent antitumor efficiency via ferroptosis but also caused little systemic toxicity in mice. All the results showed that NP-DNs would be a promising prodrug in precision-targeted ferroptosis therapy.
引用
收藏
页码：4184 / 4192
页数：9
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