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Osteoarthritis (OA), a widespread degenerative disease characterized by cartilage destruction, has emerged as a public health challenge in the current aging society. In addition to applied steroids and surgery, near-infrared (NIR) sensitive nano-enzyme for the treatment of osteoarthritis through mitochondrial repair and cartilage protection is attractive and promising. In this study, a NIR sensitive multifunctional heterostructure (EGCG (Epigallocatechin gallate) decorated Au-Ag nano-jars (E@Au-Ag)) was introduced as an enzyme-sensitive active nanoplatform for the treatment of osteoarthritis. Molecular biology results indicated that E@Au-Ag possesses intrinsic properties of anti-oxidative stress and was able to reduce the apoptosis rate of chondrocytes by 83.3%. The area of the intra-articular joint cavity injected with E@Au-Ag can be elevated to 46.6 °C under NIR to promote the release of EGCG further to induce cartilage regeneration. X-ray radiography and section staining showed that E@Au-Ag reduced cartilage damage and decreased OARSI scores by approximately 52% after 8 weeks of treatment in a surgically induced OA model. The results demonstrated that this multifunctional enzyme-like nanoplatform with a synergistic NIR sensitive property to facilitate cartilage migration and regeneration repair provides a promising OA treatment strategy. 1. NIR-sensitive nano-enzyme is gaining much attention in the field of biomedical materials. 2. EGCG decorated Au-Ag nano-heterostructures were utilized as NIR-sensitive nano-enzymes for the treatment of osteoarthritis through mitochondrial repair and cartilage protection. 3. The obtained multifunctional Au-Ag nano-heterostructures are promising for osteoarthritis treatment. [Display omitted] [ABSTRACT FROM AUTHOR]

• Photocatalytic and photothermal bifunctional nanozyme for treating osteoarthritis. • Gold-modified PCN hybrid nanozyme loaded with TP repairs damaged mitochondria. • The obtained materials promote cartilage regeneration and ameliorating joint wear. 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. [ABSTRACT FROM AUTHOR]