超分子自组装多酚纳米粒子通过抑制软骨细胞铁凋亡来缓解骨关节炎
Supramolecular self-assembled polyphenol nanoparticles alleviate osteoarthritis by inhibiting chondrocyte ferroptosis.
摘要(中文译文)
骨关节炎（OA）是一种退行性关节疾病，目前尚无治愈性疗法。近年研究表明，铁死亡参与了骨关节炎中软骨退变和炎症的进展，使其成为潜在的治疗靶点。在此，我们报道了表没食子儿茶素没食子酸酯-脯氨酸多酚纳米药物（EP NDs）的合成，该纳米药物通过表没食子儿茶素没食子酸酯（EGCG）与脯氨酸（Pro）之间的曼尼希缩合反应制备，随后自组装而成，旨在通过抑制铁死亡来减缓疾病进展。实验表明，EP NDs具有强效的自由基清除活性，能够有效清除自由基（DPPH、ABTS、·OH、O₂·⁻），并降低软骨细胞内活性氧（ROS）水平。此外，EP NDs显著抑制了氧化应激诱导的谷胱甘肽过氧化物酶4（GPX4）下调，恢复了铁稳态，减轻了脂质过氧化，并维持了线粒体功能，从而缓解了铁死亡条件下软骨细胞的代谢功能障碍。此外，EP NDs表现出优异的抗炎和免疫调节特性，促进巨噬细胞从M1型向M2型极化。转录组分析显示，EP NDs上调NRF2信号通路并下调MAPK通路，有助于抑制铁死亡并延缓OA进展。在OA大鼠模型中，EP NDs有效减轻了铁死亡，缓解了炎症，并发挥了显著的软骨保护作用。总体而言，这些研究结果表明，EP NDs通过协同的抗铁死亡、抗氧化、抗炎和免疫调节机制增强软骨保护，从而为OA提供了一种简单、高效且具有前景的治疗方法。
Abstract
Osteoarthritis (OA) is a degenerative joint disease with no currently available curative treatments. Recent studies have implicated ferroptosis in the progression of cartilage degradation and inflammation in OA, highlighting it as a potential therapeutic target. Here, we report the synthesis of epigallocatechin gallate-proline polyphenolic nanodrugs (EP NDs), prepared via a Mannich condensation reaction between epigallocatechin gallate (EGCG) and proline (Pro), followed by self-assembly, aiming to attenuate disease progression through the suppression of ferroptosis. experiments demonstrated that EP NDs possess potent free radical scavenging activity, effectively scavenging free radicals (DPPH, ABTS, ·OH, O ·) and reducing intracellular reactive oxygen species (ROS) levels in chondrocytes. Furthermore, EP NDs significantly suppressed oxidative stress-induced downregulation of glutathione peroxidase 4 (GPX4), restored iron homeostasis, attenuated lipid peroxidation, and preserved mitochondrial function, thereby alleviating metabolic dysfunction in chondrocytes under ferroptotic conditions. Additionally, EP NDs exhibited excellent anti-inflammatory and immunomodulatory properties, promoting the polarization of macrophages from the M1 to the M2 phenotype. Transcriptomic analysis revealed that EP NDs upregulated the NRF2 signaling pathway while downregulating the MAPK pathway, contributing to ferroptosis inhibition and delayed OA progression. In a rat model of OA, EP NDs effectively mitigated ferroptosis, alleviated inflammation, and exerted significant chondroprotective effects. In general, these findings demonstrate that EP NDs enhance cartilage protection through synergistic -ferroptotic, antioxidant, anti-inflammatory, and immunomodulatory mechanisms, thereby presenting a simple, efficient, and promising therapeutic approach for OA.
如何引用
AMA
Zijian Wu, Guang Shi, Luhao Li, Zhenzhou Piao, Zhuowen Hao, Renxin Chen, et al. Supramolecular self-assembled polyphenol nanoparticles alleviate osteoarthritis by inhibiting chondrocyte ferroptosis.. Materials today. Bio. 2026; doi:10.1016/j.mtbio.2026.103270.
APA
Zijian Wu, Guang Shi, Luhao Li, Zhenzhou Piao, Zhuowen Hao, Renxin Chen, et al (2026). Supramolecular self-assembled polyphenol nanoparticles alleviate osteoarthritis by inhibiting chondrocyte ferroptosis.. Materials today. Bio. https://doi.org/10.1016/j.mtbio.2026.103270
GB/T 7714
Zijian Wu, Guang Shi, Luhao Li, Zhenzhou Piao, Zhuowen Hao, Renxin Chen, et al. Supramolecular self-assembled polyphenol nanoparticles alleviate osteoarthritis by inhibiting chondrocyte ferroptosis.[J]. Materials today. Bio, 2026 doi:10.1016/j.mtbio.2026.103270.
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