摘要
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 siTNFαact as not only the gene therapeutics to inhibit TNFαproduction 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 siTNFαto macrophages followed by the significant reduction of TNFαexpression,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.
基金
supported by the National Natural Science Foundation of China(81930099,82073785,82130102,92159304,81773664)
the Natural Science Foundation of Jiangsu Province(BK20212011,China)
“Double First-Class”University project(CPU2018GY47,China)
111 Project from the Ministry of Education of China
the State Administration of Foreign Expert Affairs of China(No.111-2-07,B17047,China)
the Open Project of State Key Laboratory of Natural Medicines(No.SKLNMZZ202223,China)。