Biomimetic Nanoparticles Inhibit the HIF-1α/iNOS/NLRP3 Pathway to Alleviate Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune disease distinguished by inflammatory synovitis. Chrysin can alleviate the inflammatory response and inhibit the progression of RA. However, unfavorable physicochemical properties and nonselective biodistribution of chrysin make it difficult to achieve good therapeutic efficacy. To address these challenges, we developed a biomimetic nanocarrier to enhance the targeted delivery of chrysin to synoviocytes, a key cellular component in RA pathology. Our nanodrug, FMPlipo@C, was engineered by integrating fibroblast-like synoviocyte (FLS) membrane proteins into chrysin-loaded liposomes. This innovative approach harnesses homologous targeting mediated by FLS membrane proteins to direct liposomes to inflamed joints, facilitating cargo release within synoviocytes. We showed that FMPlipo@C reduces inflammation in collagen-induced rheumatoid arthritis (CIA) model mice by inhibiting the HIF-1α/iNOS/NLRP3 pathway, protecting cartilage, and preventing bone erosion, thus reducing swelling and stiffness. This study offers valuable insights into the development of novel therapeutic strategies for the treatment of RA.