Tetrahedral Framework Nucleic Acid Loaded miR‐23b Inhibits Synovial Inflammation and Cartilage Matrix Degradation in the Treatment of Rheumatoid Arthritis

Abstract

AbstractRheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial inflammation that eventually leads to joint destruction. Treatment for RA primarily consists of cytokine inhibitors, B cell‐depleting agents, and T cell costimulatory blocking agents. In recent years, miRNAs have come into play with better therapeutic results and less side effects, yet their clinical use is often limited by their structural instability. By incorporating miR‐23b into the structure of tFNAs to form a complex named T‐23b, the stability of miR‐23b is enhanced, allowing for an efficient delivery in the organism to fully exert its therapeutic effect. At the histological level, T‐23b treatment alleviates synovial inflammation by inhibiting the infiltration of inflammatory cells and suppressing synovial hyperplasia. It also prohibits pathologic angiogenesis, cartilage matrix degradation, and osteoclast generation to protect joint structures. At the cellular level, it inhibits the migration of synovial fibroblasts and also the synthesis and secretion of inflammatory and osteoclastic factors. At the transcriptional level, T‐23b can regulate the expression of related genes, leading to improvement in the phenotypes associated with the aforementioned disease. These effects are significantly more pronounced compared to the individual effects of miR‐23b and tFNAs respectively, making T‐23b a potential alternative for treating RA in the future.