Promoting chondrogenesis by targeted delivery to the degenerating cartilage in early treatment of osteoarthritis
Osteoarthritis (OA) is a highly incident total joint degenerative disease with cartilage degeneration as the primary pathogenesis. The cartilage matrix is mainly composed of collagen, a matrix protein with a hallmark triple-helix structure, which unfolds with collagen degradation on the cartilage surface. A collagen hybridizing peptide (CHP) is a synthetic peptide that binds the denatured collagen triple helix, conferring a potential disease-targeting possibility for early-stage OA. Here, we constructed an albumin nanoparticle (An) conjugated with CHP, loaded with a chondrogenesis-promoting small molecule drug, kartogenin (KGN). The CHP-KGN-An particle exhibited sustained release of KGN in vitro and prolonged in vivo retention selectively within the degenerated cartilage in the knee joints of model mice with early-stage OA. Compared to treatment with KGN alone, CHP-KGN-An robustly attenuated cartilage degradation, synovitis, osteophyte formation, and subchondral bone sclerosis in OA model mice and exhibited a more prominent effect on physical activity improvement and pain alleviation. Our study showcases that targeting the degenerated cartilage by collagen hybridization can remarkably promote the efficacy of small molecule drugs and may provide a novel delivery strategy for early-stage OA therapeutics.
Authors
- Xiyu Liu (ORCID: https://orcid.org/0000-0002-8788-8633)
- Ruiyang Jiang (ORCID: https://orcid.org/0000-0002-4926-2111)
- Jingjing Fan (ORCID: https://orcid.org/0000-0002-1110-5735)
- Xunhao Wang (ORCID: https://orcid.org/0000-0001-5323-196X)
- X. Li (ORCID: https://orcid.org/0000-0002-3005-8612)
- Xiaoyu Jin
- Yuxiang Fei
- Nuo Xu (ORCID: https://orcid.org/0000-0001-7429-701X)
- Dongquan Shi (ORCID: https://orcid.org/0000-0002-4769-7816)
- Weitong Li (ORCID: https://orcid.org/0000-0003-3267-3085)
- Zhaofeng Zhang (ORCID: https://orcid.org/0000-0003-1797-7507)
- Huan Liu (ORCID: https://orcid.org/0000-0002-0253-647X)
- Jiaqi Chen (ORCID: https://orcid.org/0000-0002-4069-193X)
- Yang Li (ORCID: https://orcid.org/0000-0003-3583-0314)
- Ya Xie
- Hu Guo (ORCID: https://orcid.org/0000-0001-7074-5508)
- Zizheng Liu (ORCID: https://orcid.org/0000-0002-3831-7068)
- Jiang Xia (ORCID: https://orcid.org/0000-0001-8112-7625)
- Chunqing Hu (ORCID: https://orcid.org/0009-0007-0839-3346)
- Zhongyang Lv (ORCID: https://orcid.org/0009-0003-1796-6979)
Institutions
- Sun Yat-sen University (CN)
- Chinese University of Hong Kong (HK)
- Nanjing General Hospital of Nanjing Military Command (CN)
- National Clinical Research Center for Digestive Diseases (CN)
- Nanjing Drum Tower Hospital (CN)
- Fifth Affiliated Hospital of Sun Yat-sen University (CN)
- Nanjing University (CN)
Publication Details
- Journal
- Bioactive Materials
- Published
- 2024-08-15
- DOI
- https://doi.org/10.1016/j.bioactmat.2024.08.004
- Citations
- 7
- Primary Topic
- Osteoarthritis Treatment and Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 3.29