Near Infrared Responsive Gold Nanorods Attenuate Osteoarthritis Progression by Targeting TRPV1

Abstract Osteoarthritis (OA) is the most common degenerative joint disease worldwide, with the main pathological manifestation of articular cartilage degeneration. It have been investigated that pharmacological activation of transient receptor potential vanilloid 1 (TRPV1) significantly alleviated cartilage degeneration by abolishing chondrocyte ferroptosis. In this work, in view of the thermal activated feature of TRPV1, Citrate‐stabilized gold nanorods (Cit‐AuNRs) is conjugated to TRPV1 monoclonal antibody (Cit‐AuNRs@Anti‐TRPV1) as a photothermal switch for TRPV1 activation in chondrocytes under near infrared (NIR) irradiation. The conjugation of TRPV1 monoclonal antibody barely affect the morphology and physicochemical properties of Cit‐AuNRs. Under NIR irradiation, Cit‐AuNRs@Anti‐TRPV1 exhibited good biocompatibility and flexible photothermal responsiveness. Intra‐articular injection of Cit‐AuNRs@Anti‐TRPV1 followed by NIR irradiation significantly activated TRPV1 and attenuated cartilage degradation by suppressing chondrocytes ferroptosis. The osteophyte formation and subchondral bone sclerosis are remarkably alleviated by NIR‐inspired Cit‐AuNRs@Anti‐TRPV1. Furthermore, the activation of TRPV1 by Cit‐AuNRs@Anti‐TRPV1 evidently improved physical activities and alleviated pain of destabilization of the medial meniscus (DMM)‐induced OA mice. The study reveals Cit‐AuNRs@Anti‐TRPV1 under NIR irradiation protects chondrocytes from ferroptosis and attenuates OA progression, providing a potential therapeutic strategy for the treatment of OA.