College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, 310058, Hangzhou, Zhejiang, P. R. China.
The First Affiliated Hospital of Medical School of Zhejiang University, 79 Qingchun Road, 310058, Hangzhou, Zhejiang, P. R. China.
Nat Commun. 2019 Jul 26;10(1):3349. doi: 10.1038/s41467-019-11269-8.
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.
免疫原性细胞死亡 (ICD) 相关的免疫原性可以通过内质网 (ER) 应激产生的活性氧 (ROS) 来引发。在这项研究中，我们生成了一种双 ER 靶向策略，以实现光动力疗法 (PDT) 光热疗法 (PTT) 免疫疗法。该纳米系统由 ER 靶向 pardaxin (FAL) 肽修饰、吲哚菁绿 (ICG) 缀合的空心金纳米球 (FAL-ICG-HAuNS) 以及携带血红蛋白 (Hb) 脂质体的氧供体 (FAL-Hb lipo) 组成，旨在逆转缺氧。与非靶向纳米系统相比，在近红外 (NIR) 光照射下，ER 靶向纳米系统会在细胞表面诱导强烈的 ER 应激和钙网织蛋白 (CRT) 暴露。CRT 是 ICD 的标志物，作为一种“吃我”信号来刺激树突状细胞的抗原呈递功能。结果，一系列免疫反应被激活，包括 CD8 T 细胞增殖和细胞毒性细胞因子的分泌。总之，ER 靶向 PDT-PTT 通过基于直接 ROS 的 ER 应激促进了 ICD 相关免疫疗法，并表现出增强的抗肿瘤功效。
