Department of NanoEngineering and Moores Cancer Center, University of California San Diego, La Jolla, CA, USA.
Nat Nanotechnol. 2018 Dec;13(12):1182-1190. doi: 10.1038/s41565-018-0254-4. Epub 2018 Sep 3.
Rheumatoid arthritis is a common chronic inflammatory disorder and a major cause of disability. Despite the progress made with recent clinical use of anti-cytokine biologics, the response rate of rheumatoid arthritis treatment remains unsatisfactory, owing largely to the complexity of cytokine interactions and the multiplicity of cytokine targets. Here, we show a nanoparticle-based broad-spectrum anti-inflammatory strategy for rheumatoid arthritis management. By fusing neutrophil membrane onto polymeric cores, we prepare neutrophil membrane-coated nanoparticles that inherit the antigenic exterior and associated membrane functions of the source cells, which makes them ideal decoys of neutrophil-targeted biological molecules. It is shown that these nanoparticles can neutralize proinflammatory cytokines, suppress synovial inflammation, target deep into the cartilage matrix, and provide strong chondroprotection against joint damage. In a mouse model of collagen-induced arthritis and a human transgenic mouse model of arthritis, the neutrophil membrane-coated nanoparticles show significant therapeutic efficacy by ameliorating joint damage and suppressing overall arthritis severity.
类风湿关节炎是一种常见的慢性炎症性疾病，也是导致残疾的主要原因。尽管最近在临床应用抗细胞因子生物制剂方面取得了进展，但类风湿关节炎的治疗反应率仍然不尽如人意，这主要归因于细胞因子相互作用的复杂性和细胞因子靶点的多样性。在这里，我们展示了一种基于纳米颗粒的广谱抗炎策略，用于类风湿关节炎的治疗。通过将中性粒细胞膜融合到聚合物核心上，我们制备了中性粒细胞膜包被的纳米颗粒，这些纳米颗粒继承了源细胞的抗原表面和相关的膜功能，使其成为中性粒细胞靶向生物分子的理想诱饵。研究表明，这些纳米颗粒可以中和促炎细胞因子，抑制滑膜炎症，靶向深入软骨基质，并提供强大的软骨保护作用，防止关节损伤。在胶原诱导性关节炎的小鼠模型和关节炎的人类转基因小鼠模型中，中性粒细胞膜包被的纳米颗粒通过改善关节损伤和抑制整体关节炎严重程度显示出显著的治疗效果。
