Abstract
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 peroxida-tion 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,con-sume glutathione(GSH),and thereby inactivate GPX-4,promoting the initiation stage and reducing ter-mination 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 con-trast 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.
基金项目
国家自然科学基金(U21A20287)
国家自然科学基金(22234003)
深圳市科技计划(JCYJ20210324140205013)
NETL
NSTL
万方数据