Zwitterionic Brush-Grafted Interfacial Bio-Lubricant Evades Complement C3-Mediated Macrophage Phagocytosis for Osteoarthritis Therapy

文献类型： 外文期刊

第一作者： Cai, Chuandong

作者： Cai, Chuandong;Wang, Luman;Wang, Lipeng;Zhang, Yingkai;Wu, Guohao;Hua, Bingxuan;Cao, Lu;Yan, Zuoqin;Yan, Zuoqin;Wang, Mingwei;Guo, Jiangtao;Stuart, Martien A. Cohen;Guo, Xuhong;Wang, Mingwei;Guo, Jiangtao;Stuart, Martien A. Cohen;Guo, Xuhong;Wang, Mingwei;Stuart, Martien A. Cohen;Guo, Xuhong;Wang, Luman

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关键词： complement C3; interface; macrophages; osteoarthritis; phagocytosis

期刊名称：ADVANCED MATERIALS （ 影响因子：26.8； 五年影响因子：28.9 ）

ISSN： 0935-9648

年卷期： 2025 年 37 卷 28 期

页码：

收录情况： SCI

摘要： Administering a bio-lubricant is a promising therapeutic approach for the treatment of osteoarthritis (OA), in particular, if it can both manage symptoms and halt disease progression. However, the clearance of these bio-lubricants mediated by synovial macrophages leads to reduced therapeutic efficiency and adverse inflammatory responses. Herein, it is shown that this process is predominantly mediated by the specific binding of complement C3 (on nanoparticle) and CD11b (on macrophage). More importantly, through a systematic evaluation of various interface modifications, a macrophage-evading nanoparticle strategy is proposed, which not only minimizes friction, but also largely suppresses C3 adsorption. It involves employing a zwitterionic poly-2-methacryloyloxyethyl phosphorylcholine (PMPC) brush layer grafted from a crosslinked gelatin core. In vitro studies demonstrate that such a nanoparticle lubricant can evade macrophage phagocytosis and further prevent the pro-inflammatory M1 polarization and subsequent harmful release of cytokines. In vivo studies show that the designed PMPC brush layer effectively mitigates synovial inflammation, alleviates OA-associated pain, and protects cartilage from degeneration, thus preventing OA progression. These findings clarify the pivotal role of complement C3-mediated macrophage recognition in nanoparticles clearance and offer a promising nanoparticle design strategy to restore joint lubrication.

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