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

Debin Zheng Jingfei Liu Limin Xie Yuhan Wang Yinghao Ding Rong Peng Min Cui Ling Wang Yongjie Zhang Chunqiu Zhang Zhimou Yang

Debin Zheng, Jingfei Liu, Limin Xie, Yuhan Wang, Yinghao Ding, Rong Peng, Min Cui, Ling Wang, Yongjie Zhang, Chunqiu Zhang, Zhimou Yang. Enzyme-instructed and mitochondria-targeting peptide self-assembly to efficiently induce immunogenic cell death[J]. 机械工程学报. doi: 10.1016/j.apsb.2021.07.005
引用本文: Debin Zheng, Jingfei Liu, Limin Xie, Yuhan Wang, Yinghao Ding, Rong Peng, Min Cui, Ling Wang, Yongjie Zhang, Chunqiu Zhang, Zhimou Yang. Enzyme-instructed and mitochondria-targeting peptide self-assembly to efficiently induce immunogenic cell death[J]. 机械工程学报. doi: 10.1016/j.apsb.2021.07.005
Debin Zheng, Jingfei Liu, Limin Xie, Yuhan Wang, Yinghao Ding, Rong Peng, Min Cui, Ling Wang, Yongjie Zhang, Chunqiu Zhang, Zhimou Yang. Enzyme-instructed and mitochondria-targeting peptide self-assembly to efficiently induce immunogenic cell death[J]. JOURNAL OF MECHANICAL ENGINEERING. doi: 10.1016/j.apsb.2021.07.005
Citation: Debin Zheng, Jingfei Liu, Limin Xie, Yuhan Wang, Yinghao Ding, Rong Peng, Min Cui, Ling Wang, Yongjie Zhang, Chunqiu Zhang, Zhimou Yang. Enzyme-instructed and mitochondria-targeting peptide self-assembly to efficiently induce immunogenic cell death[J]. JOURNAL OF MECHANICAL ENGINEERING. doi: 10.1016/j.apsb.2021.07.005

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

doi: 10.1016/j.apsb.2021.07.005
基金项目: 

This work was 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) and the Tianjin Science Fund for Distinguished Young Scholars (17JCJQJC44900, China). We also thank Dr. Wenjing Li and Dr. Zhiwen Hu for their help in this work.

详细信息
    通讯作者:

    Yongjie Zhang,E-mail:zhangyongjie@njmu.edu.cn

    Chunqiu Zhang,E-mail:zhangcq@nankai.edu.cn

    Zhimou Yang,E-mail:yangzm@nankai.edu.cn

  • 中图分类号: https://www.sciencedirect.com/science/article/pii/S2211383521002549/pdf?md5=b0112dbd2daef385ca3e0f9d0f453284&pid=1-s2.0-S2211383521002549-main.pdf

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

Funds: 

This work was 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) and the Tianjin Science Fund for Distinguished Young Scholars (17JCJQJC44900, China). We also thank Dr. Wenjing Li and Dr. Zhiwen Hu for their help in this work.

  • 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.

     

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出版历程
  • 收稿日期:  2021-05-07
  • 修回日期:  2021-06-02
  • 录用日期:  2021-06-29
  • 网络出版日期:  2023-03-17

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