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

• Published in: Nature communications Vol. 14; no. 1; p. 944
• Main Authors: Han, Haobo, Xing, Jiakai, Chen, Wenqi, Jia, Jiaxin, Li, Quanshun
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 20.02.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 42/109; 42/44; 631/250/24/1313; 631/250/2504/342; 631/250/38; 631/61/350/354; 631/61/391/1914; 64/60; 64/86; 82/51; 96/2; 96/31; Animals; Apoptosis; Arthritis; Arthritis, Experimental - drug therapy; Arthritis, Experimental - genetics; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - genetics; Autoimmune diseases; Carrier Proteins; Cartilage; Dendrimers; Fluorination; Health services; Humanities and Social Sciences; Inflammatory diseases; Inflammatory response; Intravenous administration; Joint diseases; Joints (anatomy); Macrophages; MicroRNAs; MicroRNAs - genetics; miRNA; multidisciplinary; Nanoparticles; Nerve Tissue Proteins; NF-κB protein; Rats; Rheumatoid arthritis; Ribonucleic acid; RNA; Science; Science (multidisciplinary); Synoviocytes; Synovium; Toxicity
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-36625-7

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-κB 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. Delivery of anti-inflammatory microRNA (miRNA) could be beneficial for inflammatory diseases such as rheumatoid arthritis (RA). Here the authors show that a fluorinated polyamidoamine dendrimer nanoparticle delivers miR-23b to affected RA joints and reduces inflammation, joint damage and synovial cell influx.