Nanozyme Loaded with Resveratrol for Osteoarthritis Therapy via Wnt/β-Catenin Pathway and Microenvironment Regulation.

Osteoarthritis (OA) is a chronic degenerative disease causing bone and cartilage deterioration, joint deformity, and functional loss. The initiation and progression of OA are primarily driven by oxidative stress and the abnormal activation of the Wnt/β-catenin signaling pathway. This study involved loading Resveratrol (Res) and platinum (Pt) nanozymes, which exhibit superoxide dismutase (SOD) and catalase (CAT), onto a metal-organic framework (MOF) due to its distinctive porosity and high loading capacity. The system was further modified with hyaluronic acid (HA) to synthesize Pt-MOF/Res@HA (PMRH) nanoparticles. The PMRH nanoparticles improve early OA prevention and treatment by concurrently inhibiting the Wnt/β-catenin signaling pathway and eliminating reactive oxygen species (ROS). Experimental results, both in vitro and in vivo, indicate that PMRH nanoparticles efficiently scavenge ROS within the OA microenvironment. The PMRH nanoparticles inhibit the overactive Wnt/β-catenin signaling pathway in chondrocytes affected by osteoarthritis. This dual-target approach, which addresses oxidative stress and inhibits the Wnt/β-catenin signaling pathway, shows promising therapeutic potential for OA.