PDF(Pubmed)
Abstract：
Rheumatoid arthritis (RA) is an autoimmune disease characterized by severe synovial inflammation and cartilage damage. Despite great progress in RA therapy, there still lacks the drugs to completely cure RA patients. Herein, we propose a reprogrammed neutrophil cytopharmaceuticals loading with TNFα-targeting-siRNA (siTNFα) as an alternative anti-inflammatory approach for RA treatment. The loaded siTNFα act as not only the gene therapeutics to inhibit TNFα production by macrophages in inflamed synovium, but also the editors to reprogram neutrophils to anti-inflammatory phenotypes. Leveraging the active tendency of neutrophils to inflammation, the reprogrammed siTNFα/neutrophil cytopharmaceuticals (siTNFα/TP/NEs) can rapidly migrate to the inflamed synovium, transfer the loaded siTNFα to macrophages followed by the significant reduction of TNFα expression, and circumvent the pro-inflammatory activity of neutrophils, thus leading to the alleviated synovial inflammation and improved cartilage protection. Our work provides a promising cytopharmaceutical for RA treatment, and puts forward a living neutrophil-based gene delivery platform.
摘要：
类风湿性关节炎（RA）是一种自身免疫性疾病，其特征是严重的滑膜炎症和软骨损伤。尽管RA治疗取得了很大进展，仍然缺乏完全治愈RA患者的药物。在这里，我们提出了一种重编程的中性粒细胞细胞药物负载TNFα靶向siRNA(siTNFα)作为RA治疗的替代抗炎方法.负载的siTNFα不仅是抑制炎症滑膜中巨噬细胞产生TNFα的基因治疗剂，而且编辑也将嗜中性粒细胞重新编程为抗炎表型。利用中性粒细胞对炎症的积极倾向，重编程的siTNFα/中性粒细胞药物（siTNFα/TP/NEs）可以快速迁移到发炎的滑膜，将加载的siTNFα转移到巨噬细胞，然后显着降低TNFα表达，规避中性粒细胞的促炎活性，从而导致减轻滑膜炎症和改善软骨保护。我们的工作为RA治疗提供了一种有前途的细胞药物，并提出了基于活中性粒细胞的基因传递平台。
