Near Infrared Responsive Gold Nanorods Attenuate Osteoarthritis Progression by Targeting TRPV1

Author:

Li Weitong12,Lv Zhongyang3,Wang Peng2,Xie Ya12,Sun Wei4,Guo Hu2,Jin Xiaoyu12,Liu Yuan2,Jiang Ruiyang5,Fei Yuxiang2,Tan Guihua2,Jiang Huiming2,Wang Xucai6,Liu Zizheng2,Wang Zheng2,Xu Nuo12,Gong Wenli12,Wu Rui2,Shi Dongquan125ORCID

Affiliation:

1. Division of Sports Medicine and Adult Reconstructive Surgery Department of Orthopedic Surgery Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine 321 Zhongshan Road Nanjing Jiangsu 210008 China

2. Division of Sports Medicine and Adult Reconstructive Surgery Department of Orthopedic Surgery Nanjing Drum Tower Hospital Affiliated Hospital of Medical School Nanjing University 321 Zhongshan Road Nanjing Jiangsu 210008 China

3. Department of Orthopedics Nanjing Jinling Hospital Affiliated Hospital of Medical School Nanjing University Nanjing 210002 China

4. Department of Orthopedic The Jiangyin Clinical College of Xuzhou Medical University Jiangyin 214400 China

5. Division of Sports Medicine and Adult Reconstructive Surgery Department of Orthopedic Surgery Nanjing Drum Tower Hospital Clinical College of Xuzhou Medical University Xuzhou Medical University Nanjing Jiangsu 221004 China

6. Co‐Innovation Center for Efficient Processing and Utilization of Forest Resources College of Chemical Engineering Nanjing Forestry University Nanjing 210037 China

Abstract

AbstractOsteoarthritis (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.

Funder

National Natural Science Foundation of China

China Postdoctoral Science Foundation

Publisher

Wiley

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