Chondrocyte membrane–coated nanoparticles promote drug retention and halt cartilage damage in rat and canine osteoarthritis

Ronghui Deng, Ruifang Zhao, Zining Zhang, Yang Chen, Meng Yang, Yixuan Lin, Jing Ye, Nan Li, Hao Qin, Xin Yan, Jian Shi, Fuzhen Yuan, Shitang Song, Zijie Xu, Yifan Song, Jiangnan Fu, Bingbing Xu, Guangjun Nie, Jia Kuo Yu

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

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.

Original languageEnglish (US)
Article numbereadh9751
JournalScience translational medicine
Volume16
Issue number735
DOIs
StatePublished - Feb 21 2024

ASJC Scopus subject areas

  • Medicine(all)

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