小鼠中通过链转移反应增强脂质过氧化用于磁共振成像指导的癌症治疗  

Enhancing lipid peroxidation via radical chain transfer reaction for MRI guided and effective cancer therapy in mice

作　　者：胥俊涛 关国强 叶知非 张成 郭义博 马原 陆畅 雷玲玲 张晓兵 宋国胜 Juntao Xu;Guoqiang Guan;Zhifei Ye;Cheng Zhang;Yibo Guo;Yuan Ma;Chang Lu;Lingling Lei;Xiao-Bing Zhanga;Guosheng Song(State Key Laboratory for Chemo/Bio-Sensing and Chemometrics,College of Chemistry and Chemical Engineering,Hunan University,Changsha 410082,China;Department of Chemistry,Case Western Reserve University,Cleveland OH 44106,USA)

机构地区：[1]State Key Laboratory for Chemo/Bio-Sensing and Chemometrics,College of Chemistry and Chemical Engineering,Hunan University,Changsha 410082,China [2]Department of Chemistry,Case Western Reserve University,Cleveland OH 44106,USA

出　　处：《Science Bulletin》2024年第5期636-647,共12页科学通报（英文版）

基　　金：supported by the National Natural Science Foundation of China(U21A20287 and 22234003);Shenzhen Science and Technology Program(JCYJ20210324140205013)。

摘　　要：Lipid peroxidation(LPO),the process of membrane lipid oxidation,is a potential new form of cell death for cancer treatment.However,the radical chain reaction involved in LPO is comprised of the initiation,propagation(the slowest step),and termination stages,limiting its effectiveness in vivo.To address this limitation,we introduce the radical chain transfer reaction into the LPO process to target the propagation step and overcome the sluggish rate of lipid peroxidation,thereby promoting endogenous lipid peroxidation and enhancing therapeutic outcomes.Firstly,radical chain transfer agent(CTA-1)/Fe nanoparticles(CTA-Fe NPs-1)was synthesized.Notably,CTA-1 convert low activity peroxyl radicals(ROO·)into high activity alkoxyl radicals(RO·),creating the cycle of free radical oxidation and increasing the propagation of lipid peroxidation.Additionally,CTA-1/Fe ions enhance reactive oxygen species(ROS)generation,consume glutathione(GSH),and thereby inactivate GPX-4,promoting the initiation stage and reducing termination of free radical reaction.CTA-Fe NPs-1 induce a higher level of peroxidation of polyunsaturated fatty acids in lipid membranes,leading to highly effective treatment in cancer cells.In addition,CTA-Fe NPs-1 could be enriched in tumors inducing potent tumor inhibition and exhibit activatable T1-MRI contrast of magnetic resonance imaging(MRI).In summary,CTA-Fe NPs-1 can enhance intracellular lipid peroxidation by accelerating initiation,propagation,and inhibiting termination step,promoting the cycle of free radical reaction,resulting in effective anticancer outcomes in tumor-bearing mice.

关 键 词：Lipid peroxidation Chain transfer reaction Cancer therapy BIOCATALYSIS 

分 类 号：R730.5[医药卫生—肿瘤]