Osteoarthritis (OA) is a chronic degenerative joint disease characterized by the degradation of articular cartilage while sustained inflammation and ferroptosis have been demonstrated to play crucial roles in the progression of OA. It is an effective strategy to fabricate nanomedicines for OA treatment. However, current research primarily concentrates on anti-inflammation, whereas nanomedicine systems for anti-ferroptosis in OA treatment are rarely reported. Additionally, there are few studies integrating inflammation inhibition with anti-ferroptosis within a single system to ameliorate OA progression. In this study, we introduce a curcumin-loaded biomimetic nanosponge (CM@Cur-NPs) to alleviate OA by synergistically suppressing inflammation and ferroptosis. CM@Cur-NPs were obtained by encapsulating curcumin within polymeric nanoparticles and coating them with macrophage cell membranes. The and synergistic anti-inflammatory and anti-ferroptotic effects of CM@Cur-NPs were investigated. It was discovered that the CM@Cur-NPs significantly reduced pro-inflammatory cytokines (TNF-α, IL-6), iNOS, ROS, and apoptosis levels of chondrocytes while concurrently increasing the anti-inflammatory cytokine (IL-4) and extracellular matrix (ECM) content . We also found that CM@Cur-NPs decreased the expression of the ferroptosis marker Fe, ACSL4, and MDA, coupled with an increase in the levels of SLC7A11 and GPX4 of chondrocytes. Lipid peroxidation of chondrocytes was attenuated by CM@Cur-NPs as well. results indicated that CM@Cur-NPs effectively alleviated OA progression and achieved cartilage protection by upregulating Aggrecan and collagen II expression, along with downregulating ADAMTS5 and MMP13 expression. This study demonstrated that CM@Cur-NPs exhibited enhanced chondroprotective effects through synergistic anti-inflammatory and anti-ferroptotic actions. It is a promising approach to integrate inflammation and ferroptosis inhibition by bioactive nanomaterials for OA treatment.

中文翻译：

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负载姜黄素的仿生纳米海绵通过协同抑制炎症和铁死亡来缓解骨关节炎


骨关节炎 (OA) 是一种慢性退行性关节疾病，其特征是关节软骨退化，而持续的炎症和铁死亡已被证明在 OA 的进展中起着至关重要的作用。制备用于治疗骨关节炎的纳米药物是一种有效的策略。然而，目前的研究主要集中在抗炎方面，而用于治疗骨关节炎的抗铁死亡的纳米药物系统却鲜有报道。此外，很少有研究将炎症抑制与抗铁死亡结合在单一系统中以改善 OA 进展。在这项研究中，我们引入了一种负载姜黄素的仿生纳米海绵（CM@Cur-NPs），通过协同抑制炎症和铁死亡来缓解 OA。 CM@Cur-NPs 是通过将姜黄素封装在聚合物纳米颗粒中并用巨噬细胞细胞膜涂覆它们而获得的。研究了 CM@Cur-NPs 的协同抗炎和抗铁死亡作用。研究发现，CM@Cur-NPs 显着降低软骨细胞的促炎细胞因子（TNF-α、IL-6）、iNOS、ROS 和凋亡水平，同时增加抗炎细胞因子（IL-4）和细胞外细胞因子的水平。基质（ECM）含量。我们还发现 CM@Cur-NPs 降低了铁死亡标记物 Fe、ACSL4 和 MDA 的表达，同时软骨细胞的 SLC7A11 和 GPX4 水平增加。 CM@Cur-NPs 也减弱了软骨细胞的脂质过氧化作用。结果表明，CM@Cur-NPs 通过上调聚集蛋白聚糖和 II 型胶原表达，同时下调 A​​DAMTS5 和 MMP13 表达，有效缓解 OA 进展并实现软骨保护。 这项研究表明，CM@Cur-NPs 通过协同抗炎和抗铁死亡作用表现出增强的软骨保护作用。通过生物活性纳米材料整合炎症和铁死亡抑制来治疗 OA 是一种很有前景的方法。