CD80 Antibody and MTX Co-Engineered Extracellular Vesicles Targets CD80+ Macrophages to Suppress Inflammation and Alleviate Chronic Inflammatory Diseases

作者：Jianhua Yang, H. Zhang, Wenzhe Wang, Qiqi Yin, Xiaoning He, Dihao Tao, Hanzhe Wang, Wenhao Liu, Yiming Wang, Zhiwei Dong, Xin Chen, Bei Li · 发表于：International Journal of Nanomedicine · 年份：2025 · DOI：10.2147/ijn.s517357 · 被引用次数：9 · 研究领域：Extracellular vesicles in disease、Immune cells in cancer、Immunotherapy and Immune Responses

Introduction: Aberrant interaction between innate immune and adaptive immune cells can disrupt tissue homeostasis, consequently triggering chronic inflammatory diseases such as rheumatoid arthritis (RA) and periodontitis (PD). Pro-inflammatory macrophages serve as critical mediators in the early immune response, constituting a major population of CD80 + cells, while anti-inflammatory macrophages modulating inflammatory processes through the secretion of transforming growth factor-beta (TGF-β). This cytokine facilitates the differentiation of peripheral regulatory T cells (Tregs) and contributes to the establishment of immune tolerance. However, there are no definitive therapies to reshape the tissue homeostasis between innate immune and adaptive immune cells. Methods: (1) anti-CD80-MTX-EVs was obtained by gradient centrifugation, which were characterized by TEM and DLS, and the associated membrane proteins were identified by Western Blot. (2) The mouse bone marrow-derived macrophages were co-cultured separately with EVs, anti-CD80-EVs, and anti-CD80-MTX-EVs in vitro, and the expression of CD80 on the macrophages surface as well as the proportion of Treg cell generation were detected. (3) EVs, anti-CD80-EVs and anti-CD80-MTX-EVs were injected into mice models of arthritis and periodontitis for treatment, the therapeutic effect was evaluated by the expressions of related cytokines, staining of HE, the proportion of CD80 + macrophages and the phenotypic differentiation of T cell...