DataVXAdvanced SciencePaper
journal article·2024-02Open access

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

Advanced Science· Volume 11· Issue 7
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Source abstract

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.
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Research context

OpenAlex topics: Extracellular vesicles in disease · Phagocytosis and Immune Regulation · Immune cells in cancer

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

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

Department of Clinical Biochemistry Faculty of Pharmacy and Laboratory Medicine Army Medical University (Third Military Medical University) Chongqing 40000 China

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

Department of Military Basic Training and Army Management Army Health Service Training Base Army Medical University (Third Military Medical University) Chongqing 400000 China

Department of Biochemistry and Molecular Biology College of Basic Medical Sciences Army Medical University (Third Military Medical University) Chongqing 400000 China

Department of Rehabilitation Medicine The First Affiliated Hospital of Chongqing Medical University Chongqing 400000 China

Center for Joint Surgery Department of Orthopedic Surgery The Second Affiliated Hospital of Chongqing Medical University Chongqing 400000 China

Funding

National Key Research and Development Program of China · National Natural Science Foundation of China · Natural Science Foundation of Chongqing

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