Mesoporous catechin nanocarriers potentiate curcumin to treat osteoarthritis via synergistic antioxidant and macrophage repolarization

Osteoarthritis (OA) is a persistent inflammatory joint disorder for which there are currently no effective therapeutic interventions. The pathogenesis of OA is intimately associated with oxidative stress and an inflammatory environment. Therefore, this study developed curcumin-loaded mesoporous catechin nanoparticles (Cur@MCN) for enhanced treatment of OA. MCN could effectively encapsulate curcumin due to their mesoporous features, thereby significantly enhancing curcumin's dispersibility and bioavailability. In vitro studies revealed that the Cur@MCN surpassed either free curcumin or MCN alone in scavenging reactive oxygen species, attenuating inflammatory responses, and protecting chondrocytes. Mechanistically, the Cur@MCN drive macrophage repolarization from the M1 (pro-inflammatory) type toward the M2 (anti-inflammatory) type via the targeted modulation of the NLR family pyrin domain-containing 3 (NLRP3) inflammasome signaling axis. In a validated Sprague-Dawley rat model of OA, intra-articular administration of Cur@MCN significantly alleviated cartilage erosion, reduced synovial inflammation, and improved OARSI histological scores, confirming its potent chondroprotective and anti-inflammatory effects. These findings indicate that Cur@MCN may be an effective therapeutic agent for treating OA and other diseases related to oxidative stress.