Synovial fibroblast‐targeting liposomes encapsulating an NF‐κB‐blocking peptide ameliorates zymosan‐induced synovial inflammation

Synovial fibroblasts (SFs) play a crucial role in the inflammatory process of rheumatoid arthritis (RA). The highly activated NF‐κB signal in SFs is responsible for most of the synovial inflammation associated with this disease. In this study, we have developed an SF‐targeting liposomal system that encapsulates the NF‐κB‐blocking peptide (NBD peptide) HAP‐lipo/NBD. HAP‐lipo/NBDs demonstrated efficient SF‐specific targeting in vitro and in vivo. Our study also showed a significant inhibitory effect of HAP‐lipo/NBD on NF‐κB activation, inflammatory cytokine release and SF migration capability after zymosan stimulation. Furthermore, the systemic administration of HAP‐lipo/NBDs significantly inhibited synovial inflammation and improved the pathological scores of arthritis induced by zymosan. Thus, these results suggest that an SF‐targeting NF‐κB‐blocking strategy is a potential approach for the development of alternative, targeted anti‐RA therapies.