Sheng Weibei, Li Aikang, Yue Yaohang, Wang Qichang, Yu Fei, Weng Jian, Lin Jianjing, Chen Yingqi, Zeng Hui, Wang Deli, Yang Jun, Liu Peng
Department of Bone & Joint Surgery, National & Local Joint Engineering Research Center of Orthopedic Biomaterials, Shenzhen Key Laboratory of Orthopedic Diseases and Biomaterials Research, Peking University Shenzhen Hospital, Shenzhen, 518036, China.
Shenzhen Xinhua Hospital, Shenzhen, 518028, China.
Macromol Rapid Commun. 2025 Apr;46(7):e2400495. doi: 10.1002/marc.202400495. Epub 2024 Sep 18.
Osteoarthritis (OA) is a chronic degenerative joint disease characterized by the degradation of articular cartilage. Recent studies have demonstrated that chondrocyte ferroptosis plays a crucial role in the progression of OA. Consequently, developing nanomedicines that suppress chondrocyte ferroptosis is a promising strategy for OA treatment. However, there are few reports on nanomedicines specifically targeting chondrocyte ferroptosis for OA therapy. In this study, Curcumin-loaded nanoparticles (Cur-NPs) are fabricated to suppress chondrocyte ferroptosis by regulating reactive oxygen species (ROS), ferrous ion (Fe⁺), and Acyl-CoA Synthetase Long-Chain Family Member 4 (ACSL4) levels of chondrocyte. This is achieved by combining the functions of curcumin and an amphiphilic block copolymer with ROS scavenging and iron-chelating properties. The in vitro anti-ferroptotic effects of Cur-NPs are thoroughly investigated. The findings indicate that Cur-NPs decrease the expression of ferroptosis markers such as ROS, Fe⁺, and ACSL4, while protecting the mitochondrial membrane potential of chondrocytes. Additionally, Cur-NPs attenuated lipid peroxidation in chondrocytes. Furthermore, Cur-NPs significantly reduced the expression of the catabolic factor Matrix Metallopeptidase 13 (MMP13) and increased the expression of the anabolic factor Collagen type II (Col II) in vitro. This study demonstrates that Cur-NPs exhibit enhanced chondroprotective effects through anti-ferroptotic actions, presenting a promising approach for inhibiting chondrocyte ferroptosis using bioactive nanomaterials in OA treatment.
骨关节炎（OA）是一种以关节软骨退变 为特征的慢性退行性关节疾病。最近的研究表明，软骨细胞铁死亡在OA的进展中起关键作用。因此，开发抑制软骨细胞铁死亡的纳米药物是一种有前景的OA治疗策略。然而，针对OA治疗专门靶向软骨细胞铁死亡的纳米药物报道较少。在本研究中，制备了负载姜黄素的纳米颗粒（Cur-NPs），通过调节软骨细胞的活性氧（ROS）、亚铁离子（Fe⁺）和酰基辅酶A合成酶长链家族成员4（ACSL4）水平来抑制软骨细胞铁死亡。这是通过将姜黄素与具有ROS清除和铁螯合特性的两亲性嵌段共聚物的功能相结合来实现的。对Cur-NPs的体外抗铁死亡作用进行了深入研究。结果表明，Cur-NPs降低了ROS、Fe⁺和ACSL4等铁死亡标志物的表达，同时保护了软骨细胞的线粒体膜电位。此外，Cur-NPs减轻了软骨细胞中的脂质过氧化。此外，Cur-NPs在体外显著降低了分解代谢因子基质金属蛋白酶13（MMP13）的表达，并增加了合成代谢因子Ⅱ型胶原（Col II）的表达。本研究表明，Cur-NPs通过抗铁死亡作用表现出增强的软骨保护作用，为在OA治疗中使用生物活性纳米材料抑制软骨细胞铁死亡提供了一种有前景的方法。
