Near-infrared Light-modulated Gold And Silver Heterostructure-loaded Epigallocatechin Gallate Promote Cartilage Repair In Osteoarthritis Rats

Objective To prepare epigallocatechin gallate(EGCG)-modified gold and silver heterostructures(E@Au-Ag)as near-infrared light-sensitive nanoenzymes.To investigate its role and mechanism in promoting cartilage regenerative properties and repairing cartilage damage in osteoarthritis.Methods Silver nanoparticles were prepared by silver nitrate and sodium borohydride,followed by the continuous addition of silver nitrate and sodium citrate to the reaction system to obtain silver nanoparticles.Then Au-Ag heterostructures were obtained by adding the tetra-chloroauric acid solution to the PVP reduction system.The elemental composition,photothermal properties,and EGCG release of E@Au-Ag were examined by transmission electron microscopy(TEM),energy spectrum analysis,ultraviolet-visible spectroscopy(UV-vis),and fluorescence emission spectroscopy.Cell proliferation migration assay,mitochondrial membrane potential assay,and collagen II expression assay were performed by primary chondrocytes.The photothermal effect was assessed in vivo by NIR irradiation after intra-articular administration in a rat osteoarthritis model.The efficacy of E@Au-Ag in rats with osteoarthritis was also evaluated by gross observation,X-ray radiographs,and tissue section staining.Finally,the potential of E@Au-Ag to prevent intra-articular infections was evaluated by in vitro inhibition rate studies of common clinical strains.Results The synthesized E@Au-Ag with NIR photosensitivity and stable photothermal effect achieved satisfactory results in repairing cartilage damage and preventing intra-articular injection infection.Under NIR light irradiation,the local area can be heated up to 46.6°C and promote the further release of loaded EGCG,which acts as a synergistic catalyst to reduce the oxidative stress microenvironment.The results showed that E@Au-Ag could reduce apoptosis of primary chondrocytes,promote migration and proliferation of chondrocytes,and upregulate type II collagen expression to exert multiple effects on cartilage repair.In addition,animal experiments showed that the cartilage wear in arthritic rats at the end of the treatment cycle was significantly improved,the cartilage layer was significantly thickened,and the OARSI score was significantly reduced.Moreover,in vitro antibacterial experiments also confirmed a significant inhibitory effect on common strains of clinical intra-articular infections.The in vitro and in vivo experimental studies showed that the prepared NIR light-sensitive E@AuAg could treat osteoarthritis through mitochondrial repair and cartilage protection,providing a new idea for the clinical treatment of osteoarthritis.Conclusions(1)Gold and silver nano-heterostructures with good photothermal properties were successfully prepared.(2)The gold-silver nano-heterostructures loaded with tea polyphenols under NIR light irradiation can effectively alleviate the oxidative stress microenvironment.(3)The gold-silver nano-heterostructures can promote the proliferation,migration,and type II collagen expression of chondrocytes and promote the repair of the cartilage layer in osteoarthritic rats.