Fei Yuxiang, Li Xiaojing, Lv Zhongyang, Liu Zizheng, Xie Ya, Chen Jiaqi, Li Weitong, Liu Xiyu, Guo Hu, Liu Huan, Zhang Zhaofeng, Wang Xunhao, Fan Jingjing, Hu Chunqing, Jin Xiaoyu, Jiang Ruiyang, Xu Nuo, Xia Jiang, Li Yang, Shi Dongquan
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, 210008, Jiangsu, PR China.
State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, Jiangsu, PR China.
Bioact Mater. 2024 Aug 15;40:624-633. doi: 10.1016/j.bioactmat.2024.08.004. eCollection 2024 Oct.
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.
骨关节炎（OA）是一种高发性的全关节退行性疾病，其主要发病机制为软骨退变。软骨基质主要由胶原蛋白组成，胶原蛋白是一种具有标志性三螺旋结构的基质蛋白，随着软骨表面胶原蛋白的降解而展开。胶原蛋白杂交肽（CHP）是一种能与变性胶原蛋白三螺旋结合的合成肽，为早期OA提供了潜在的疾病靶向治疗可能性。在此，我们构建了一种与CHP偶联的白蛋白纳米颗粒（An），并负载了一种促进软骨生成的小分子药物——卡托金（KGN）。CHP-KGN-An颗粒在体外表现出KGN的持续释放，并在早期OA模型小鼠膝关节退变软骨中选择性地延长了体内保留时间。与单独使用KGN治疗相比，CHP-KGN-An显著减轻了OA模型小鼠的软骨降解、滑膜炎、骨赘形成和软骨下骨硬化，并在改善身体活动和减轻疼痛方面表现出更显著的效果。我们的研究表明，通过胶原蛋白杂交靶向退变软骨可显著提高小分子药物的疗效，并可能为早期OA治疗提供一种新的给药策略。
