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Chondrocyte membrane-coated nanoparticles promote drug retention and halt cartilage damage in rat and canine osteoarthritis.
Deng, Ronghui; Zhao, Ruifang; Zhang, Zining; Chen, Yang; Yang, Meng; Lin, Yixuan; Ye, Jing; Li, Nan; Qin, Hao; Yan, Xin; Shi, Jian; Yuan, Fuzhen; Song, Shitang; Xu, Zijie; Song, Yifan; Fu, Jiangnan; Xu, Bingbing; Nie, Guangjun; Yu, Jia-Kuo.
Afiliación
  • Deng R; Department of Sports Medicine, Peking University Third Hospital, Institute of Sports Medicine of Peking University, Beijing 100191, P. R. China.
  • Zhao R; CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center of Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, P. R. China.
  • Zhang Z; Beijing Key Laboratory of Sports Injuries, Beijing 100191, P. R. China.
  • Chen Y; CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center of Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, P. R. China.
  • Yang M; Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, P. R. China.
  • Lin Y; Department of Sports Medicine, Peking University Third Hospital, Institute of Sports Medicine of Peking University, Beijing 100191, P. R. China.
  • Ye J; Beijing Key Laboratory of Sports Injuries, Beijing 100191, P. R. China.
  • Li N; CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center of Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, P. R. China.
  • Qin H; Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, P. R. China.
  • Yan X; Department of Sports Medicine, Peking University Third Hospital, Institute of Sports Medicine of Peking University, Beijing 100191, P. R. China.
  • Shi J; Beijing Key Laboratory of Sports Injuries, Beijing 100191, P. R. China.
  • Yuan F; CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center of Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, P. R. China.
  • Song S; Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, P. R. China.
  • Xu Z; Department of Sports Medicine, Peking University Third Hospital, Institute of Sports Medicine of Peking University, Beijing 100191, P. R. China.
  • Song Y; Beijing Key Laboratory of Sports Injuries, Beijing 100191, P. R. China.
  • Fu J; CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center of Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, P. R. China.
  • Xu B; Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, P. R. China.
  • Nie G; CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center of Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, P. R. China.
  • Yu JK; Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, P. R. China.
Sci Transl Med ; 16(735): eadh9751, 2024 Feb 21.
Article en En | MEDLINE | ID: mdl-38381849
ABSTRACT
Osteoarthritis (OA) is a chronic joint disease characterized by progressive degeneration of articular cartilage. A challenge in the development of disease-modifying drugs is effective delivery to chondrocytes. The unique structure of the joint promotes rapid clearance of drugs through synovial fluid, and the dense and avascular cartilage extracellular matrix (ECM) limits drug penetration. Here, we show that poly(lactide-co-glycolic acid) nanoparticles coated in chondrocyte membranes (CM-NPs) were preferentially taken up by rat chondrocytes ex vivo compared with uncoated nanoparticles. Internalization of the CM-NPs was mediated primarily by E-cadherin, clathrin-mediated endocytosis, and micropinocytosis. These CM-NPs adhered to the cartilage ECM in rat knee joints in vivo and penetrated deeply into the cartilage matrix with a residence time of more than 34 days. Simulated synovial fluid clearance studies showed that CM-NPs loaded with a Wnt pathway inhibitor, adavivint (CM-NPs-Ada), delayed the catabolic metabolism of rat and human chondrocytes and cartilage explants under inflammatory conditions. In a surgical model of rat OA, drug-loaded CM-NPs effectively restored gait, attenuated periarticular bone remodeling, and provided chondroprotection against cartilage degeneration. OA progression was also mitigated by CM-NPs-Ada in a canine model of anterior cruciate ligament transection. These results demonstrate the feasibility of using chondrocyte membrane-coated nanoparticles to improve the pharmacokinetics and efficacy of anti-OA drugs.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteoartritis / Cartílago Articular / Nanopartículas Límite: Animals / Humans Idioma: En Revista: Sci Transl Med Asunto de la revista: CIENCIA / MEDICINA Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteoartritis / Cartílago Articular / Nanopartículas Límite: Animals / Humans Idioma: En Revista: Sci Transl Med Asunto de la revista: CIENCIA / MEDICINA Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos