Cross between doctors and practitioners in rheumatoid arthritis —— miR-30a delivery mediated by fluorinated dendrimers can regulate the inflammation of macrophages and alleviate the symptoms of rheumatoid arthritis

This article is selected:The abnormal expression of microRNA (miRNAs) plays an important role in the pathogenesis of rheumatoid arthritis (RA), so mirna-based therapy has become a promising method for RA treatment. Here, miR-30a was successfully screened and identified as an important mediator of RA inflammation. MiR-30a can directly target Snai1 gene, further regulate the expression of Cad11, inhibit NF-κB and MAPK signaling pathways, and contribute to anti-inflammatory. In order to improve the therapeutic effect of miR-30a, fluorinated polyamidoamine dendrimer (FP) was developed as a carrier to realize the delivery of miR-30a in collagen-induced arthritis mice. Vector FP and miR-30a form a stable nanocomposite, which effectively mediates the transfection of miR-30a and performs anti-inflammatory reaction in macrophages stimulated by lipopolysaccharide. In addition, the intravenous administration of FP/miR-30a shows obvious accumulation in the inflamed joints, and inhibits the inflammatory reaction through the Snai1/Cad11 axis, thus contributing to the anti-arthritis effect. In addition, FP/miR-30a nanocomposites show good biocompatibility because they will not cause organ damage after systemic administration. To sum up, our research shows that miR-30a is an effective anti-inflammatory oligonucleotide, and the delivery of miR-30a mediated by fluorinated dendrimer may become a promising method to treat RA and other autoimmune diseases.

Innovations: 1. The precise regulation mechanism of miR-30a in rheumatoid arthritis was systematically revealed for the first time, which provided a new molecular target for inflammatory regulation by directly targeting Snai1 gene and regulating the expression of Cad11; 2. The fluorinated polyamidoamine dendrimer (FP) was innovatively developed as the delivery carrier of miRNA, which broke through the technical bottleneck of traditional nucleic acid delivery and significantly improved the targeted delivery efficiency of miR-30a. 3. Through the construction of nanocomposites, the stable delivery of miR-30a in vivo was realized, which overcame the inherent limitations of easy degradation and difficult transport of small molecular RNA. 4. The unique advantages of FP/miR-30a nanocomposites in inhibiting NF-κB and MAPK signaling pathways were proved for the first time, which provided a new therapeutic idea for autoimmune diseases.

Scientific research inspiration: 1. Reveals the important regulatory role of microRNA in autoimmune diseases, and provides a new molecular target and research direction for precision medicine; 2. It shows the great potential of interdisciplinary research between doctors and workers, and solves the key technical problems in the biomedical field through the integration of material science and biology; 3. It proves the great application prospect of nano-delivery technology in gene therapy and provides technical support for personalized therapy; 4. A new targeted intervention strategy for diseases is provided, and the importance of precise regulation at molecular level is emphasized.

Extension of ideas: 1. The technology platform can be extended to other autoimmune diseases, such as systemic lupus erythematosus and multiple sclerosis; 2. Explore the regulatory mechanisms of different types of microRNA in diseases, and build a more comprehensive molecular regulatory network; 3. Optimize the structure of nano-delivery carrier, improve targeting and biocompatibility, and realize more accurate gene therapy; 4. Combining gene editing technology, such as CRISPR-Cas9, to further improve the accuracy and efficiency of miRNA treatment; 5. Expand the research scope and explore the potential application of miRNA in tumor immunity, neurodegenerative diseases and other fields; 6. Develop more diversified nano-delivery materials to improve the transport efficiency of different types of nucleic acid molecules; 7. Establish a more systematic and standardized evaluation system for miRNA therapy, and promote gene therapy from laboratory to clinic.

DOI : 10.1016/j.jconrel.2024.11.009