Study on the anti-inflammatory effect of tetrahedral framework nucleic acid-loaded sinomenine in the treatment of rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by destructive and symmetrical joint lesions and joint synovitis, with the main clinical manifestations including joint deformity, morning stiffness, and inflammation in the joints of the hands, feet, wrists and ankles, and the temporomandibular joints. Sinomenine is a natural alkaloid with anti-inflammatory, analgesic, immunosuppressive and bone-protective effects, showing great potential in the treatment of rheumatoid arthritis. However, sinomenine suffers from drawbacks such as poor water solubility, low bioavailability and rapid degradation, which compromise its therapeutic efficacy. Tetrahedral framework nucleic acid (TFNA) is a DNA nanostructure with excellent delivery capacity for small-molecule drugs. It can bind small molecules from traditional Chinese medicine through electrostatic interactions and groove binding, thereby improving bioavailability. In this study, using TFNA as a carrier, we constructed a drug delivery system with favorable stability and biocompatibility – the TFNA–SIN complex – to deliver SIN into synovial fibroblasts, exerting anti-inflammatory effects and inhibiting cell proliferation. TFNA–SIN inhibits the expression of M1 macrophages, promotes the expression of M2 macrophages, and suppresses inflammatory cell infiltration by blocking the NF-κB and extracellular regulated protein kinase (ERK) signaling pathways. Therefore, TFNA improves the bioavailability of SIN and reduces SIN-induced toxicity, representing a promising alternative agent for the treatment of RA.