NIR triggered photocatalytic and photothermal bifunctional MOF nanozyme using for improving osteoarthritis microenvironment by repairing injured chondrocytes of mitochondria

Osteoarthritis (OA) is one of the leading causes of chronic disability in the elderly. Effective clinical interventions for OA are still lacking, and new therapeutic measures are urgently needed. The emerging near-infrared light (NIR) sensitive nanozymes are attractive for their great potential and appeal in treating OA by repairing mitochondrial function and improving impaired autophagic flux. In this study, a NIR-sensitive tea polyphenol-modified zirconium-based porphyrin metal–organic framework (TP-Au@PCN) was introduced as a multifunctional nanoplatform for the treatment of OA. TEM and EDS mapping revealed that gold nanoclusters were uniformly distributed on the surface of the spherical particles. Electron spin resonance (ESR) analysis revealed that nanozymes could alleviate different types of oxidative stress. Molecular biology indicated that TP-Au@PCN reduced chondrocyte apoptosis and increased chondrocyte metabolism by 80.7%. An increase in chondrocyte-expressed type II collagen and proteoglycan content ensues. Injection of TP-Au@PCN effectively raised the joint temperature to 46.9 °C and controlled drug delivery under NIR excitation. Section staining revealed that eight weeks of intervention decreased the OARSI score in OA rats by approximately 67.0%. Transmission electron microscopy confirmed a significant improvement in intracellular mitochondrial morphology. The present study provides evidence that modifiable multifunctional nanozymes effectively repair cartilage-damaged mitochondria and promote cartilage regeneration, representing an appealing therapeutic strategy for OA.