癌症免疫疗法
内质网
免疫疗法
免疫系统
未折叠蛋白反应
癌症
癌细胞
肿瘤微环境
癌症研究
细胞生物学
化学
纳米技术
免疫学
生物
材料科学
遗传学
作者
Zhanzhan Zhang,Zheng Pan,Qiushi Li,Hui Qi,Linqi Shi,Yang Liu
出处
期刊:Science Advances
[American Association for the Advancement of Science (AAAS)]
日期:2024-02-09
卷期号:10 (6)
被引量:2
标识
DOI:10.1126/sciadv.adk0716
摘要
Nanoparticle-based cancer immunotherapy has shown promising therapeutic potential in clinical settings. However, current research mainly uses nanoparticles as delivery vehicles but overlooks their potential to directly modulate immune responses. Inspired by the endogenous endoplasmic reticulum (ER) stress caused by unfolded/misfolded proteins, we present a rationally designed immunogenic cell death (ICD) inducer named NanoICD, which is a nanoparticle engineered for ER targeting and retention. By carefully controlling surface composition and properties, we have obtained NanoICD that can effectively accumulate in the ER, induce ER stress, and activate ICD-associated immune responses. In addition, NanoICD is generally applicable to various proteins and enzymes to further enhance the immunomodulatory capacity, exemplified by encapsulating catalase (CAT) to obtain NanoICD/CAT, effectively alleviated immunosuppressive tumor microenvironment and induced robust antitumor immune responses in 4T1-bearing mice. This work demonstrates engineered nanostructures’ potential to autonomously regulate biological processes and provides insights into the development of advanced nanomedicines for cancer treatment.
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