Fluorinated polyamidoamine dendrimer-mediated miR-23b delivery for the treatment of experimental rheumatoid arthritis in rats

被引:16
|
作者
Han, Haobo [1 ]
Xing, Jiakai [1 ]
Chen, Wenqi [1 ]
Jia, Jiaxin [1 ]
Li, Quanshun [1 ]
机构
[1] Jilin Univ, Sch Life Sci, Key Lab Mol Enzymol & Engn, Minist Educ, Changchun 130012, Peoples R China
基金
国家重点研发计划; 中国国家自然科学基金;
关键词
NF-KAPPA-B; BLOCKING INTERLEUKIN-1; TREATING INFLAMMATION; NONVIRAL VECTORS; GENE DELIVERY; THERAPY; MIGRATION; EFFICIENT; PROTEIN;
D O I
10.1038/s41467-023-36625-7
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
In rheumatoid arthritis (RA), insufficient apoptosis of macrophages and excessive generation of pro-inflammatory cytokines are intimately connected, accelerating the development of disease. Here, a fluorinated polyamidoamine dendrimer (FP) is used to deliver miR-23b to reduce inflammation by triggering the apoptosis of as well as inhibiting the inflammatory response in macrophages. Following the intravenous injection of FP/miR-23b nanoparticles in experimental RA models, the nanoparticles show therapeutic efficacy with inhibition of inflammatory response, reduced bone and cartilage erosion, suppression of synoviocyte infiltration and the recovery of mobility. Moreover, the nanoparticles accumulate in the inflamed joint and are non-specifically captured by synoviocytes, leading to the restoration of miR-23b expression in the synovium. The miR-23b nanoparticles target Tab2, Tab3 and Ikka to regulate the activation of NF-kappa B pathway in the hyperplastic synovium, thereby promoting anti-inflammatory and anti-proliferative responses. Additionally, the intravenous administration of FP/miR-23b nanoparticles do not induce obvious systemic toxicity. Overall, our work demonstrates that the combination of apoptosis induction and inflammatory inhibition could be a promising approach in the treatment of RA and possibly other autoimmune diseases.
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页数:20
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