Advanced Science (Feb 2024)
A Novel Cargo Delivery System‐AnCar‐ExoLaIMTS Ameliorates Arthritis via Specifically Targeting Pro‐Inflammatory Macrophages
- Song Li,
- Ya‐ran Wu,
- Xiu‐qin Peng,
- Han‐gang Chen,
- Tong‐yi Zhang,
- Hua Chen,
- Jing Yang,
- Yang‐li Xie,
- Hua‐bing Qi,
- Wei Xiang,
- Bo Huang,
- Si‐ru Zhou,
- Yan Hu,
- Qiao‐yan Tan,
- Xiao‐lan Du,
- Jun‐lan Huang,
- Ruo‐bin Zhang,
- Xiao‐hong Li,
- Feng‐tao Luo,
- Min Jin,
- Nan Su,
- Xiao‐qing Luo,
- Shuo Huang,
- Peng Yang,
- Xiao‐Jing Yan,
- Ji‐qin Lian,
- Ying Zhu,
- Yan Xiong,
- Gong‐yi Xiao,
- Ying‐ying Liu,
- Chen Shen,
- Liang Kuang,
- Zhen‐hong Ni,
- Lin Chen
Affiliations
- Song Li
- Center of Bone Metabolism and repair laboratory for Prevention and rehabilitation of Training injuries State Key laboratory of Trauma Burns and combined injury Trauma center Research Institute of Surgery Daping Hospital Army Medical University (Third Military Medical University) Chongqing 400000 China
- Ya‐ran Wu
- Department of Clinical Biochemistry Faculty of Pharmacy and Laboratory Medicine Army Medical University (Third Military Medical University) Chongqing 40000 China
- Xiu‐qin Peng
- Center of Bone Metabolism and repair laboratory for Prevention and rehabilitation of Training injuries State Key laboratory of Trauma Burns and combined injury Trauma center Research Institute of Surgery Daping Hospital Army Medical University (Third Military Medical University) Chongqing 400000 China
- Han‐gang Chen
- Center of Bone Metabolism and repair laboratory for Prevention and rehabilitation of Training injuries State Key laboratory of Trauma Burns and combined injury Trauma center Research Institute of Surgery Daping Hospital Army Medical University (Third Military Medical University) Chongqing 400000 China
- Tong‐yi Zhang
- State Key Laboratory of Trauma Burns and Combined Injury Department of Rehabilitation Medicine Daping Hospital Army Medical University (Third Military Medical University) Chongqing 400000 China
- Hua Chen
- Center of Bone Metabolism and repair laboratory for Prevention and rehabilitation of Training injuries State Key laboratory of Trauma Burns and combined injury Trauma center Research Institute of Surgery Daping Hospital Army Medical University (Third Military Medical University) Chongqing 400000 China
- Jing Yang
- Center of Bone Metabolism and repair laboratory for Prevention and rehabilitation of Training injuries State Key laboratory of Trauma Burns and combined injury Trauma center Research Institute of Surgery Daping Hospital Army Medical University (Third Military Medical University) Chongqing 400000 China
- Yang‐li Xie
- Center of Bone Metabolism and repair laboratory for Prevention and rehabilitation of Training injuries State Key laboratory of Trauma Burns and combined injury Trauma center Research Institute of Surgery Daping Hospital Army Medical University (Third Military Medical University) Chongqing 400000 China
- Hua‐bing Qi
- Center of Bone Metabolism and repair laboratory for Prevention and rehabilitation of Training injuries State Key laboratory of Trauma Burns and combined injury Trauma center Research Institute of Surgery Daping Hospital Army Medical University (Third Military Medical University) Chongqing 400000 China
- Wei Xiang
- State Key Laboratory of Trauma Burns and Combined Injury Department of Rehabilitation Medicine Daping Hospital Army Medical University (Third Military Medical University) Chongqing 400000 China
- Bo Huang
- State Key Laboratory of Trauma Burns and Combined Injury Department of Rehabilitation Medicine Daping Hospital Army Medical University (Third Military Medical University) Chongqing 400000 China
- Si‐ru Zhou
- Center of Bone Metabolism and repair laboratory for Prevention and rehabilitation of Training injuries State Key laboratory of Trauma Burns and combined injury Trauma center Research Institute of Surgery Daping Hospital Army Medical University (Third Military Medical University) Chongqing 400000 China
- Yan Hu
- Department of Military Basic Training and Army Management Army Health Service Training Base Army Medical University (Third Military Medical University) Chongqing 400000 China
- Qiao‐yan Tan
- Center of Bone Metabolism and repair laboratory for Prevention and rehabilitation of Training injuries State Key laboratory of Trauma Burns and combined injury Trauma center Research Institute of Surgery Daping Hospital Army Medical University (Third Military Medical University) Chongqing 400000 China
- Xiao‐lan Du
- Center of Bone Metabolism and repair laboratory for Prevention and rehabilitation of Training injuries State Key laboratory of Trauma Burns and combined injury Trauma center Research Institute of Surgery Daping Hospital Army Medical University (Third Military Medical University) Chongqing 400000 China
- Jun‐lan Huang
- Center of Bone Metabolism and repair laboratory for Prevention and rehabilitation of Training injuries State Key laboratory of Trauma Burns and combined injury Trauma center Research Institute of Surgery Daping Hospital Army Medical University (Third Military Medical University) Chongqing 400000 China
- Ruo‐bin Zhang
- Center of Bone Metabolism and repair laboratory for Prevention and rehabilitation of Training injuries State Key laboratory of Trauma Burns and combined injury Trauma center Research Institute of Surgery Daping Hospital Army Medical University (Third Military Medical University) Chongqing 400000 China
- Xiao‐hong Li
- Center of Bone Metabolism and repair laboratory for Prevention and rehabilitation of Training injuries State Key laboratory of Trauma Burns and combined injury Trauma center Research Institute of Surgery Daping Hospital Army Medical University (Third Military Medical University) Chongqing 400000 China
- Feng‐tao Luo
- Center of Bone Metabolism and repair laboratory for Prevention and rehabilitation of Training injuries State Key laboratory of Trauma Burns and combined injury Trauma center Research Institute of Surgery Daping Hospital Army Medical University (Third Military Medical University) Chongqing 400000 China
- Min Jin
- Center of Bone Metabolism and repair laboratory for Prevention and rehabilitation of Training injuries State Key laboratory of Trauma Burns and combined injury Trauma center Research Institute of Surgery Daping Hospital Army Medical University (Third Military Medical University) Chongqing 400000 China
- Nan Su
- Center of Bone Metabolism and repair laboratory for Prevention and rehabilitation of Training injuries State Key laboratory of Trauma Burns and combined injury Trauma center Research Institute of Surgery Daping Hospital Army Medical University (Third Military Medical University) Chongqing 400000 China
- Xiao‐qing Luo
- Center of Bone Metabolism and repair laboratory for Prevention and rehabilitation of Training injuries State Key laboratory of Trauma Burns and combined injury Trauma center Research Institute of Surgery Daping Hospital Army Medical University (Third Military Medical University) Chongqing 400000 China
- Shuo Huang
- Center of Bone Metabolism and repair laboratory for Prevention and rehabilitation of Training injuries State Key laboratory of Trauma Burns and combined injury Trauma center Research Institute of Surgery Daping Hospital Army Medical University (Third Military Medical University) Chongqing 400000 China
- Peng Yang
- Center of Bone Metabolism and repair laboratory for Prevention and rehabilitation of Training injuries State Key laboratory of Trauma Burns and combined injury Trauma center Research Institute of Surgery Daping Hospital Army Medical University (Third Military Medical University) Chongqing 400000 China
- Xiao‐Jing Yan
- Department of Biochemistry and Molecular Biology College of Basic Medical Sciences Army Medical University (Third Military Medical University) Chongqing 400000 China
- Ji‐qin Lian
- Department of Clinical Biochemistry Faculty of Pharmacy and Laboratory Medicine Army Medical University (Third Military Medical University) Chongqing 40000 China
- Ying Zhu
- Department of Rehabilitation Medicine The First Affiliated Hospital of Chongqing Medical University Chongqing 400000 China
- Yan Xiong
- Center of Bone Metabolism and repair laboratory for Prevention and rehabilitation of Training injuries State Key laboratory of Trauma Burns and combined injury Trauma center Research Institute of Surgery Daping Hospital Army Medical University (Third Military Medical University) Chongqing 400000 China
- Gong‐yi Xiao
- Center for Joint Surgery Department of Orthopedic Surgery The Second Affiliated Hospital of Chongqing Medical University Chongqing 400000 China
- Ying‐ying Liu
- Center of Bone Metabolism and repair laboratory for Prevention and rehabilitation of Training injuries State Key laboratory of Trauma Burns and combined injury Trauma center Research Institute of Surgery Daping Hospital Army Medical University (Third Military Medical University) Chongqing 400000 China
- Chen Shen
- Center of Bone Metabolism and repair laboratory for Prevention and rehabilitation of Training injuries State Key laboratory of Trauma Burns and combined injury Trauma center Research Institute of Surgery Daping Hospital Army Medical University (Third Military Medical University) Chongqing 400000 China
- Liang Kuang
- Center of Bone Metabolism and repair laboratory for Prevention and rehabilitation of Training injuries State Key laboratory of Trauma Burns and combined injury Trauma center Research Institute of Surgery Daping Hospital Army Medical University (Third Military Medical University) Chongqing 400000 China
- Zhen‐hong Ni
- State Key Laboratory of Trauma Burns and Combined Injury Department of Rehabilitation Medicine Daping Hospital Army Medical University (Third Military Medical University) Chongqing 400000 China
- Lin Chen
- Center of Bone Metabolism and repair laboratory for Prevention and rehabilitation of Training injuries State Key laboratory of Trauma Burns and combined injury Trauma center Research Institute of Surgery Daping Hospital Army Medical University (Third Military Medical University) Chongqing 400000 China
- DOI
- https://doi.org/10.1002/advs.202306143
- Journal volume & issue
-
Vol. 11,
no. 7
pp. n/a – n/a
Abstract
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‐ExoLaIMTS. The data indicate that the phagocytosis efficiencies of pro‐inflammatory macrophages for different AnCar‐ExoLaIMTS show obvious differences. The AnCar‐ExoLaIMTS3 has the best targeting ability for pro‐inflammatory macrophages in vitro and in vivo. Mechanically, AnCar‐ExoLaIMTS3 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‐ExoLaIMTS3 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‐inflammatory macrophages, which may be beneficial for the treatments of arthritis and other inflammatory diseases.
Keywords
