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

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-inflammatory macrophages, which may be beneficial for the treatments of arthritis and other inflammatory diseases.

SUBMITTER: Li S

PROVIDER: S-EPMC10870055 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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A Novel Cargo Delivery System-AnCar-Exo<sup>LaIMTS</sup> Ameliorates Arthritis via Specifically Targeting Pro-Inflammatory Macrophages.

Li Song S Wu Ya-Ran YR Peng Xiu-Qin XQ Chen Han-Gang HG Zhang Tong-Yi TY Chen Hua H Yang Jing J Xie Yang-Li YL Qi Hua-Bing HB Xiang Wei W Huang Bo B Zhou Si-Ru SR Hu Yan Y Tan Qiao-Yan QY Du Xiao-Lan XL Huang Jun-Lan JL Zhang Ruo-Bin RB Li Xiao-Hong XH Luo Feng-Tao FT Jin Min M Su Nan N Luo Xiao-Qing XQ Huang Shuo S Yang Peng P Yan Xiao-Jing XJ Lian Ji-Qin JQ Zhu Ying Y Xiong Yan Y Xiao Gong-Yi GY Liu Ying-Ying YY Shen Chen C Kuang Liang L Ni Zhen-Hong ZH Chen Lin L

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20231211 7

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 ...[more]

PMID: 38083984

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

Publications

A Novel Cargo Delivery System-AnCar-Exo<sup>LaIMTS</sup> Ameliorates Arthritis via Specifically Targeting Pro-Inflammatory Macrophages.

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A Novel Cargo Delivery System-AnCar-ExoLaIMTS Ameliorates Arthritis via Specifically Targeting Pro-Inflammatory Macrophages.

Publications

A Novel Cargo Delivery System-AnCar-Exo<sup>LaIMTS</sup> Ameliorates Arthritis via Specifically Targeting Pro-Inflammatory Macrophages.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

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