Reprogrammed siTNFα/neutrophil cytopharmaceuticals targeting inflamed joints for rheumatoid arthritis therapy.
10.1016/j.apsb.2022.08.012
- Author:
Yijun CHEN
1
;
Kaiming LI
1
;
Mengying JIAO
1
;
Yingshuang HUANG
1
;
Zihao ZHANG
1
;
Lingjing XUE
1
;
Caoyun JU
1
;
Can ZHANG
1
Author Information
1. State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, China Pharmaceutical University, Nanjing 210009, China.
- Publication Type:Journal Article
- Keywords:
Anti-inflammatory;
Cartilage protection;
Gene delivery;
Macrophages;
Neutrophil cytopharmaceuticals;
Rheumatoid arthritis;
Tumor necrosis factor α;
siRNA
- From:
Acta Pharmaceutica Sinica B
2023;13(2):787-803
- CountryChina
- Language:English
-
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.
