Targeted and MMP-2/9 responsive peptides for the treatment of rheumatoid arthritis

Bioactive peptides are attractive candidates for drug development. QAW is a tripeptide that is obtained from an anti-inflammatory protein-Annexin A1 (ANXA1). Previous studies showed that QAW alleviated inflammation in experimental colitis and inflammatory bowel disease via NF-κB inhibition. This study establishes adjuvant-induced arthritis (AIA) mouse models and explores the anti-inflammatory efficacy of QAW in AIA mice. To enhance the targeting, responsiveness, and efficacy of QAW to inflammation, QAW (Q) is modified with a cell penetrating peptide (T), a matrix metalloproteases-2/9 (MMP-2/9) digestive peptide (M), and an inflammation targeting peptide-RGD (R). The designed RMTQ demonstrates enhanced delivery to cytoplasm, higher reduction of pro-inflammatory factors, and better efficacy than QAW. The anti-inflammatory efficacy of RMTQ is similar to that of DEX in this study whereas RMTQ treatment shows a higher safety than that of DEX. In sum, this study demonstrates that RMTQ can be a potential therapeutic for inflammatory arthritis.