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Targeting photodynamic and photothermal therapy to the endoplasmic reticulum enhances immunogenic cancer cell death

Author

Listed:
  • Wei Li

    (Zhejiang University)

  • Jie Yang

    (Zhejiang University)

  • Lihua Luo

    (Zhejiang University)

  • Mengshi Jiang

    (Zhejiang University)

  • Bing Qin

    (Zhejiang University)

  • Hang Yin

    (Zhejiang University)

  • Chunqi Zhu

    (Zhejiang University)

  • Xiaoling Yuan

    (Zhejiang University)

  • Junlei Zhang

    (Zhejiang University)

  • Zhenyu Luo

    (Zhejiang University)

  • Yongzhong Du

    (Zhejiang University)

  • Qingpo Li

    (Zhejiang University)

  • Yan Lou

    (The First Affiliated Hospital of Medical School of Zhejiang University)

  • Yunqing Qiu

    (The First Affiliated Hospital of Medical School of Zhejiang University)

  • Jian You

    (Zhejiang University)

Abstract

Immunogenic cell death (ICD)-associated immunogenicity can be evoked through reactive oxygen species (ROS) produced via endoplasmic reticulum (ER) stress. In this study, we generate a double ER-targeting strategy to realize photodynamic therapy (PDT) photothermal therapy (PTT) immunotherapy. This nanosystem consists of ER-targeting pardaxin (FAL) peptides modified-, indocyanine green (ICG) conjugated- hollow gold nanospheres (FAL-ICG-HAuNS), together with an oxygen-delivering hemoglobin (Hb) liposome (FAL-Hb lipo), designed to reverse hypoxia. Compared with non-targeting nanosystems, the ER-targeting naosystem induces robust ER stress and calreticulin (CRT) exposure on the cell surface under near-infrared (NIR) light irradiation. CRT, a marker for ICD, acts as an ‘eat me’ signal to stimulate the antigen presenting function of dendritic cells. As a result, a series of immunological responses are activated, including CD8+ T cell proliferation and cytotoxic cytokine secretion. In conclusion, ER-targeting PDT-PTT promoted ICD-associated immunotherapy through direct ROS-based ER stress and exhibited enhanced anti-tumour efficacy.

Suggested Citation

  • Wei Li & Jie Yang & Lihua Luo & Mengshi Jiang & Bing Qin & Hang Yin & Chunqi Zhu & Xiaoling Yuan & Junlei Zhang & Zhenyu Luo & Yongzhong Du & Qingpo Li & Yan Lou & Yunqing Qiu & Jian You, 2019. "Targeting photodynamic and photothermal therapy to the endoplasmic reticulum enhances immunogenic cancer cell death," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11269-8
    DOI: 10.1038/s41467-019-11269-8
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    Cited by:

    1. Minglun Liu & Yuncong Chen & Yan Guo & Hao Yuan & Tongxiao Cui & Shankun Yao & Suxing Jin & Huanhuan Fan & Chengjun Wang & Ran Xie & Weijiang He & Zijian Guo, 2022. "Golgi apparatus-targeted aggregation-induced emission luminogens for effective cancer photodynamic therapy," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    2. Ke-Fei Xu & Shun-Yu Wu & Zihao Wang & Yuxin Guo & Ya-Xuan Zhu & Chengcheng Li & Bai-Hui Shan & Xinping Zhang & Xiaoyang Liu & Fu-Gen Wu, 2024. "Hyperbaric oxygen enhances tumor penetration and accumulation of engineered bacteria for synergistic photothermal immunotherapy," Nature Communications, Nature, vol. 15(1), pages 1-21, December.

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