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.