Teo Kristeen Ye Wen, Sevencan Cansu, Cheow Yi Ann, Zhang Shipin, Leong David Tai, Toh Wei Seong
Faculty of Dentistry National University Centre for Oral Health National University of Singapore 9 Lower Kent Ridge Road, #10-01 Singapore 119085 Singapore.
Department of Chemical and Biomolecular Engineering Faculty of Engineering National University of Singapore 4 Engineering Drive 4 Singapore 117585 Singapore.
Small Sci. 2022 Jan 29;2(4):2100116. doi: 10.1002/smsc.202100116. eCollection 2022 Apr.
Osteoarthritis (OA) is a chronic degenerative joint disorder associated with pain and inflammation, and is the leading cause of disability worldwide. Owing to the complexity of OA inflammation driven by a plethora of inflammatory cytokines, current specific anti-cytokine therapies have not been successful. Among the immune cells implicated in OA inflammation, macrophages reportedly regulate OA inflammation via macrophage polarization. Given that pro-inflammatory M1 and anti-inflammatory M2 macrophages have opposing roles in OA inflammation, exploiting advanced polarization of macrophages to specific macrophage subsets (M0, M1, and M2) to enhance the therapeutic efficacy of macrophage membrane-coated gold (Au) nanoparticles (NPs) as a broad-spectrum anti-inflammatory agent for OA treatment is proposed. Herein, it is shown that among the macrophage membrane-coated NPs generated from the various macrophage subsets, M2 macrophage membrane-coated nanoparticles (Au-M2 NPs) uniquely exhibit superior efficacy in sponging the pro-inflammatory cytokines and alleviating OA inflammation and matrix degradation over its counterparts derived from the same macrophage cell source, in both inflammation-stimulated chondrocyte and explant OA models. Collectively, the herein described results validate macrophage polarization as a facile strategy to enhance the therapeutic efficacy of macrophage membrane NP-based immunotherapy for potential OA treatment.
骨关节炎（OA）是一种与疼痛和炎症相关的慢性退行性关节疾病，是全球范围内导致残疾的主要原因。由于多种炎症细胞因子驱动的OA炎症的复杂性，目前的特异性抗细胞因子疗法尚未取得成功。在与OA炎症相关的免疫细胞中，据报道巨噬细胞通过巨噬细胞极化来调节OA炎症。鉴于促炎性M1巨噬细胞和抗炎性M2巨噬细胞在OA炎症中具有相反的作用，本文提出利用巨噬细胞向特定巨噬细胞亚群（M0、M1和M2）的高级极化，来提高巨噬细胞膜包被金（Au）纳米颗粒（NPs）作为OA治疗的广谱抗炎剂的治疗效果。在此表明，在由各种巨噬细胞亚群产生的巨噬细胞膜包被的NPs中，M2巨噬细胞膜包被的纳米颗粒（Au-M2 NPs）在炎症刺激的软骨细胞和外植体OA模型中，在清除促炎性细胞因子以及减轻OA炎症和基质降解方面，比源自相同巨噬细胞来源的对应物具有独特的卓越功效。总体而言，本文所述结果证实巨噬细胞极化是一种简便的策略，可提高基于巨噬细胞膜NP的免疫疗法对潜在OA治疗的疗效。
