Nanomedicines targeting matrix metalloproteinases for osteoarthritis treatment.

Osteoarthritis (OA) is a frequently diagnosed joint disease. It is characterized by articular cartilage/bone damage, synovitis, pain, etc., which severely reduce the life quality of patients. Current treatments for OA act to reduce inflammation and lubricate joints but barely halt OA progression and joint damage. Matrix metalloproteinases (MMPs) are key factors for extracellular matrix (ECM)/cartilage/bone degradation and inflammation. Therapies targeting MMPs hold the potential to treat OA efficiently. Recently, MMPs have been studied as the therapeutic targets for OA treatment. MMP inhibitors, gene therapies for MMP silencing, and biological agents for MMP clearance are continuously reported. However, these therapies are limited by short intra-articular drug retention, insufficient joint targeting, low bioavailability, etc. To solve these issues, nanomedicines have been reported to improve MMP-targeted therapies. To highlight the advances in this field, this review first introduces the key subtypes and biological roles of MMPs in OA pathogenesis. It then summarizes the reported MMP-targeted therapies and the advanced nanomedicines that improved the MMP-targeted therapies. Finally, it discusses the mechanisms, progress, issues, and the future perspectives of the nanomedicines for the MMP-targeted therapies.