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

Acta Pharmaceutica Sinica B

Zhimou Yang¹  Chunqiu Zhang²  Ling Wang³  Yinghao Ding³  Min Cui⁴  Yongjie Zhang⁴  Rong Peng⁵  Debin Zheng⁵  Jingfei Liu⁵  Limin Xie⁵  Yuhan Wang⁵ 

[1] [phone] (Chunqiu Zhang and Zhimou Yang).;Corresponding authors. Tel./fax: [phone] (Yongjie Zhang);College of Pharmacy, Nankai University, Tianjin 300071, China;Department of Human Anatomy, Nanjing Medical University, Nanjing 211166, China;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;

关键词: Immunogenic cell death;    Self-assembly;    Mitochondria targeting;    Enzyme;   

DOI  :  

来源: DOAJ

【 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 photosensitizer-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.

【 授权许可】

Unknown