Huang Kui, Li Qiumei, Lin Huixuan, Shen Qian, Wu Yaping, Tian Taoran, Ma Chuan, Shi Sirong, Xiao Jingang, Lin Yunfeng
Department of Oral and Maxillofacial Surgery, The Affiliated Stomatological Hospital of Southwest Medical University, Luzhou, 646002, China.
State Key Laboratory of Oral Diseases National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China.
Adv Sci (Weinh). 2025 Jul;12(26):e2502661. doi: 10.1002/advs.202502661. Epub 2025 Apr 7.
Osteoarthritis (OA) is a chronic joint disease that causes a gradual deterioration of articular cartilage. A major challenge in OA treatment is the limited penetration and delivery efficiency of drugs to cartilage and chondrocytes due to the rapid clearance of drugs through synovial fluid in joints and the osmotic barrier of the cartilage extracellular matrix (ECM). To address this issue, a novel tetrahedral framework nucleic acid (tFNA)-based nanomedicine delivery system (tFNA-2WL) is first synthesized with excellent cartilage permeability and perfect chondrocyte endocytosis properties. After being loaded with ginsenoside Rb1 (Gin), the tFNA-2WL&Gin complex not only penetrates the cartilage but also accumulates in the menisci, ligaments, and joint capsules, thus prolonging the residence time of Gin in OA rat knees. In vitro, tFNA-2WL&Gin effectively promotes chondrogenesis, inhibits cartilage degradation by reducing apoptosis, and scavenges reactive oxygen species (ROS), outperforming free Gin. In OA rats, tFNA-2WL&Gin restores gait, reduces osteophyte formation, inhibits synovial inflammation and hypertrophy, and protects cartilage from further damage more effectively than Gin and other nanomedicines. These results demonstrate the feasibility of tFNA-2WL in improving the pharmacokinetics and efficacy of drugs and highlight the favorable curative effects of tFNA-2WL&Gin for OA, offering a promising paradigm for translational medicine.
骨关节炎（OA）是一种慢性关节疾病，会导致关节软骨逐渐退化。OA治疗中的一个主要挑战是，由于药物通过关节滑液的快速清除以及软骨细胞外基质（ECM）的渗透屏障，药物对软骨和软骨细胞的渗透及递送效率有限。为了解决这个问题，首先合成了一种新型的基于四面体框架核酸（tFNA）的纳米药物递送系统（tFNA - 2WL），其具有优异的软骨渗透性和完美的软骨细胞内吞特性。负载人参皂苷Rb1（Gin）后，tFNA - 2WL&Gin复合物不仅能穿透软骨，还能在半月板、韧带和关节囊中蓄积，从而延长Gin在OA大鼠膝关节中的停留时间。在体外，tFNA - 2WL&Gin能有效促进软骨生成，通过减少细胞凋亡抑制软骨降解，并清除活性氧（ROS），其效果优于游离Gin。在OA大鼠中，tFNA - 2WL&Gin能恢复步态，减少骨赘形成，抑制滑膜炎症和肥大，并且比Gin和其他纳米药物更有效地保护软骨免受进一步损伤。这些结果证明了tFNA - 2WL在改善药物药代动力学和疗效方面的可行性，并突出了tFNA - 2WL&Gin对OA的良好治疗效果，为转化医学提供了一个有前景的范例。
