A Novel Cargo Delivery System-AnCar-Exo<SUP>LaIMTS</SUP> Ameliorates Arthritis via Specifically Targeting Pro-Inflammatory Macrophages
作者全名："Li, Song; Wu, Ya-ran; Peng, Xiu-qin; Chen, Han-gang; Zhang, Tong-yi; Chen, Hua; Yang, Jing; Xie, Yang-li; Qi, Hua-bing; Xiang, Wei; Huang, Bo; Zhou, Si-ru; Hu, Yan; Tan, Qiao-yan; Du, Xiao-lan; Huang, Jun-lan; Zhang, Ruo-bin; Li, Xiao-hong; Luo, Feng-tao; Jin, Min; Su, Nan; Luo, Xiao-qing; Huang, Shuo; Yang, Peng; Yan, Xiao-Jing; Lian, Ji-qin; Zhu, Ying; Xiong, Yan; Xiao, Gong-yi; Liu, Ying-ying; Shen, Chen; Kuang, Liang; Ni, Zhen-hong; Chen, Lin"
作者地址："[Li, Song; Peng, Xiu-qin; Chen, Han-gang; Chen, Hua; Yang, Jing; Xie, Yang-li; Qi, Hua-bing; Zhou, Si-ru; Tan, Qiao-yan; Du, Xiao-lan; Huang, Jun-lan; Zhang, Ruo-bin; Li, Xiao-hong; Luo, Feng-tao; Jin, Min; Su, Nan; Luo, Xiao-qing; Huang, Shuo; Yang, Peng; Xiong, Yan; Liu, Ying-ying; Shen, Chen; Kuang, Liang; Chen, Lin] Third Mil Med Univ, Army Med Univ, Daping Hosp, Res Inst Surg,Ctr Bone Metab & Repair,Trauma Ctr,L, Chongqing 400000, Peoples R China; [Wu, Ya-ran; Lian, Ji-qin] Third Mil Med Univ, Army Med Univ, Fac Pharm & Lab Med, Dept Clin Biochem, Chongqing 40000, Peoples R China; [Zhang, Tong-yi; Xiang, Wei; Huang, Bo; Ni, Zhen-hong] Third Mil Med Univ, Army Med Univ, Daping Hosp, Dept Rehabil Med, Chongqing 400000, Peoples R China; [Hu, Yan] Third Mil Med Univ, Army Med Univ, Dept Mil Basic Training & Army Management, Army Hlth Serv Training Base, Chongqing 400000, Peoples R China; [Yan, Xiao-Jing] Third Mil Med Univ, Army Med Univ, Coll Basic Med Sci, Dept Biochem & Mol Biol, Chongqing 400000, Peoples R China; [Zhu, Ying] Chongqing Med Univ, Affiliated Hosp 1, Dept Rehabil Med, Chongqing 400000, Peoples R China; [Xiao, Gong-yi; Shen, Chen] Chongqing Med Univ, Affiliated Hosp 2, Ctr Joint Surg, Dept Orthoped Surg, Chongqing 400000, Peoples R China"
通信作者："Kuang, L; Chen, L (通讯作者)，Third Mil Med Univ, Army Med Univ, Daping Hosp, Res Inst Surg,Ctr Bone Metab & Repair,Trauma Ctr,L, Chongqing 400000, Peoples R China.; Ni, ZH (通讯作者)，Third Mil Med Univ, Army Med Univ, Daping Hosp, Dept Rehabil Med, Chongqing 400000, Peoples R China."
来源：ADVANCED SCIENCE
ESI学科分类：PHYSICS
WOS号：WOS:001123664800001
JCR分区：Q1
影响因子：14.3
年份：2023
卷号：
期号：
开始页：
结束页：
文献类型：Article; Early Access
关键词：arthritis; exosome; HIF-1 alpha
摘要："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-1 alpha level, thus ameliorating the severity of arthritis in vivo. Collectively, the work established a novel gene/drug delivery system that can specifically target pro-inflammatory macrophages, which may be beneficial for the treatments of arthritis and other inflammatory diseases."
基金机构："National Key Research and Development Program of China [2018YFA0800802]; National Natural Science Youth Foundation of China [82002360]; National Natural Science Foundation of China [81830075, 81871817, 82372495, 82202770]; Natural Science Foundation of Chongqing [CSTB2022NSCQ-MSX1267]; Army medical university project [2021XQN22]; General Project of Chongqing Natural Science Foundation [cstc2020jcyj-msxmX0112]"
基金资助正文："This study was supported by National Key Research and Development Program of China (2018YFA0800802), National Natural Science Youth Foundation of China (82002360), the National Natural Science Foundation of China (81830075, 81871817, 82372495, 82202770), Natural Science Foundation of Chongqing (No.CSTB2022NSCQ-MSX1267), army medical university project (2021XQN22) and the General Project of Chongqing Natural Science Foundation (No. cstc2020jcyj-msxmX0112) We acknowledge the drawing tool online (Figdraw)."
