A Novel Cargo Delivery System‐AnCar‐Exo LaIMTS Ameliorates Arthritis via Specifically Targeting Pro‐Inflammatory Macrophages

作者：Song Li, Yaran Wu, Xiuqin Peng, Hangang Chen, Tong‐Yi Zhang, Hua Chen, Jing Yang, Yangli Xie, Huabing Qi, Wei Xiang, Bo Huang, Siru Zhou, Yan Hu, Qiaoyan Tan, Xiaolan Du, Junlan Huang, R. Zhang, Xiaohong Li, Fengtao Luo, Min Jin, Nan Su, Xiaoqing Luo, Shuo Huang, Yang Peng, Xiao‐Jing Yan, Jiqin Lian, Ying Zhu, Yan Xiong, Gongyi Xiao, Ying‐ying Liu, Chen Shen, Liang Kuang, Zhenhong Ni, Lin Chen · 发表于：Advanced Science · 年份：2023 · DOI：10.1002/advs.202306143 · 被引用次数：7 · 研究领域：Extracellular vesicles in disease、Phagocytosis and Immune Regulation、Immune cells in cancer

Abstract Macrophages are heterogenic phagocytic cells that play distinct roles in physiological and pathological processes. Targeting different types of macrophages has shown potent therapeutic effects in many diseases. Although many approaches are developed to target anti‐inflammatory macrophages, there are few researches on targeting pro‐inflammatory macrophages, which is partially attributed to their non‐s pecificity phagocytosis of extracellular substances. In this study, a novel recombinant protein is constructed that can be anchored on an exosome membrane with the purpose of targeting pro‐inflammatory macrophages via antigen recognition, which is named AnCar‐Exo LaIMTS . The data indicate that the phagocytosis efficiencies of pro‐inflammatory macrophages for different AnCar‐Exo LaIMTS show obvious differences. The AnCar‐Exo LaIMTS3 has the best targeting ability for pro‐inflammatory macrophages in vitro and in vivo. Mechanically, AnCar‐Exo LaIMTS3 can specifically recognize the leucine‐rich repeat domain of the TLR4 receptor, and then enter into pro‐inflammatory macrophages via the TLR4‐mediated receptor endocytosis pathway. Moreover, AnCar‐Exo LaIMTS3 can efficiently deliver therapeutic cargo to pro‐inflammatory macrophages and inhibit the synovial inflammatory response via downregulation of HIF‐1α level, thus ameliorating the severity of arthritis in vivo. Collectively, the work established a novel gene/drug delivery system that can specifically target pro‐inflammator...