Enzyme-instructed and mitochondria-targeting peptide self-assembly to efficiently induce immunogenic cell death

查看全文 作　　者：Debin [1]Zheng;Jingfei [1]Liu;Limin [1]Xie;Yuhan [1]Wang;Yinghao [2]Ding;Rong [1]Peng;Min [3]Cui;Ling [2]Wang;Yongjie [3]Zhang;Chunqiu [1]Zhang;Zhimou [1]Yang

机构地区：[1]Key Laboratory of Bioactive Materials,Ministry of Education,State Key Laboratory of Medicinal Chemical Biology,College of Life Sciences,Collaborative Innovation Center of Chemical Science and Engineering,National Institute of Functional Materials,Nankai University,Tianjin 300071,China;[2]College of Pharmacy,Nankai University,Tianjin 300071,China;[3]Department of Human Anatomy,Nanjing Medical University,Nanjing 211166,China

出　　处：《Acta Pharmaceutica Sinica B》索引2022年第12卷第6期,共11页

基　　金：supported by the National Natural Science Foundation of China (31870949,21875116,31961143004,81921004,81100942,81472081);the National Science Fund for Distinguished Young Scholars (31825012,China);the Tianjin Science Fund for Distinguished Young Scholars (17JCJQJC44900,China)。 摘　　要：Immunogenic cell death(ICD) plays a major role in cancer immunotherapy by stimulating specific T cell responses and restoring the antitumor immune system.However,effective type Ⅱ ICD inducers without biotoxicity are still very limited.Herein,a tentative drug-or photo sensitizer-free strategy was developed by employing enzymatic self-assembly of the peptide F-pY-T to induce mitochondrial oxidative stress in cancer cells.Upon dephosphorylation catalyzed by alkaline phosphatase overexpressed on cancer cells,the peptide F-pY-T self-assembled to form nanoparticles,which were subsequently internalized.These affected the morphology of mitochondria and induced serious reactive oxygen species production,causing the ICD characterized by the release of danger-associated molecular patterns(DAMPs).DAMPs enhanced specific immune responses by promoting the maturation of DCs and the intratumoral infiltration of tumor-specific T cells to eradicate tumor cells.The dramatic immunotherapeutic capacity could be enhanced further by combination therapy of F-pY-T and anti-PD-L1 agents without visible biotoxicity in the main organs.Thus,our results revealed an alternative strategy to induce efficient ICD by physically promoting mitochondrial oxidative stress. 关键词：Immunogenic cell death SELF-ASSEMBLY Mitochondria targeting ENZYME

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Enzyme-instructed and mitochondria-targeting peptide self-assembly to efficiently induce immunogenic cell death

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