Targeting photodynamic and photothermal therapy to the endoplasmic reticulum enhances immunogenic cancer cell death
By Wei Li, Lihua Luo, Mengshi Jiang, Bing Qin, Hang Yin, Chunqi Zhu, Xiaoling Yuan, Junlei Zhang, Zhenyu Luo, Yongzhong Du and 4 more. Nature Communications, 2019
915 citations recorded by the source corpus.
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. Reactive oxygen species induced by endoplasmic reitculum stress can be exploited for cancer therapy. Here, nanoparticles are targetted to the endoplasmic reticulum and, when accompanied by PDT, produce stress resulting in calreticulin exposure on the cell surface, which activates dendritic cells.
Subfields: Biomedical Engineering, Cell Biology, Immunology
View Paper: https://www.semanticscholar.org/paper/3282d2fd55411ac7b846c7debb49b68c560ee193
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- Yajun Wang
- T. Gong
- Meihui He
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Citations in the corpus
- Nanomedicine in cancer therapy (2023, background): “Consequently, the activated dendritic cells triggered an array of immune responses, such as the proliferation of CD8+ T cells and the release of cytotoxic cytokines, and thus improved anti-tumor efficacy.(449) TCPP-T.”
- Endoplasmic reticulum stress: molecular mechanism and therapeutic targets (2023, background): “An ER-targeting nanosystem consisting of ERtargeting pardaxin peptides modified with indocyanine green conjugated hollow gold nanospheres together with an oxygendelivering hemoglobin liposome has giant prospects.(412) Reversing activated ER stress in CD8 T cells helps the production of antitumor CD8”