Magnetic Field-Actuated ZIF-8-Encapsulated Fe₃O₄ Nanoparticles Attenuate Osteoarthritis via Antioxidant Effects

Osteoarthritis (OA), characterized by oxidative stress and inflammatory damage, poses significant challenges in achieving effective local drug concentrations and sustaining reactive oxygen species (ROS) clearance. This study developed a nanoparticle, Fe₃O₄@ZIF-8, endowed with superoxide dismutase (SOD)- and catalase (CAT)-like enzyme-mimetic activities. The nanocomposite not only synergistically neutralizes key ROS but also significantly alleviates oxidative stress and inflammatory responses in chondrocytes by modulating SIRT1/Nrf2 axis. More importantly, the introduction of an external magnetic field (MF) was demonstrated to markedly enhance cellular uptake and retention of the nanoparticles, thereby providing superior cartilage protection and tissue repair compared to non-targeted intervention. Macroscopic and histological evaluations confirmed that the cartilage morphology and matrix composition in the Fe₃O₄@ZIF-8 + MF group closely resembled those of healthy tissue, accompanied by notable downregulation of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and catabolic enzymes (MMP-3, MMP-13). These findings highlight the potential of magnetically guided nanozyme therapy as a novel and efficacious approach for OA treatment, offering a multimodal solution to modulate the disease microenvironment and enhance regenerative outcomes.