Yu Haichao, Song Zelong, Yu Jie, Ren Boyuan, Dong Yuan, You Yonggang, Zhang Zhen, Jia Chengqi, Zhao Yunpeng, Zhou Xuhui, Sun Haifeng, Zhang Xuesong
School of Medicine, Nankai University, Tianjin 300071, China.
Department of Orthopaedics, The Fourth Medical Center of PLA General Hospital, Beijing 100048, China.
Bioact Mater. 2023 Oct 7;32:164-176. doi: 10.1016/j.bioactmat.2023.09.020. eCollection 2024 Feb.
Osteoarthritis (OA) has emerged as a significant health concern among the elderly population, with increasing attention paid to ferroptosis-induced OA in recent years. However, the prolonged use of nonsteroidal anti-inflammatory drugs or corticosteroids can lead to a series of side effects and limited therapeutic efficacy. This study aimed to employ the Mannich condensation reaction between epigallocatechin-3-gallate (EGCG) and selenomethionine (SeMet) to efficiently synthesize polyphenol-based nanodrugs in aqueous media for treating OA. Molecular biology experiments demonstrated that EGCG-based nanodrugs (ES NDs) could effectively reduce glutathione peroxidase 4 (GPX4) inactivation, abnormal Fe accumulation, and lipid peroxidation induced by oxidative stress, which ameliorated the metabolic disorder of chondrocytes and other multiple pathological processes triggered by ferroptosis. Moreover, imaging and histopathological analysis of the destabilization of the medial meniscus model in mice confirmed that ES NDs exhibiting significant therapeutic effects in relieving OA. The intra-articular delivery of ES NDs represents a promising approach for treating OA and other joint inflammatory diseases.
骨关节炎（OA）已成为老年人群中一个重要的健康问题，近年来，铁死亡诱导的OA受到越来越多的关注。然而，长期使用非甾体抗炎药或皮质类固醇会导致一系列副作用且治疗效果有限。本研究旨在利用表没食子儿茶素-3-没食子酸酯（EGCG）和硒代蛋氨酸（SeMet）之间的曼尼希缩合反应，在水性介质中高效合成用于治疗OA的基于多酚的纳米药物。分子生物学实验表明，基于EGCG的纳米药物（ES NDs）可以有效减少氧化应激诱导的谷胱甘肽过氧化物酶4（GPX4）失活、异常铁积累和脂质过氧化，从而改善软骨细胞的代谢紊乱以及铁死亡引发的其他多种病理过程。此外，对小鼠内侧半月板模型不稳定的成像和组织病理学分析证实，ES NDs在缓解OA方面具有显著的治疗效果。ES NDs的关节内给药是治疗OA和其他关节炎症性疾病的一种有前景的方法。
