Uveitis comprises a cluster of intraocular inflammatory disorders characterized by uncontrolled autoimmune responses and excessive oxidative stress leading to vision loss worldwide. In the present study, curcumin (CUR) was conjugated with polyvinylpyrrolidone (PVP) to form PVP-CUR nanoparticles with significantly elevated solubility and outstanding multiple radical scavenging abilities. studies revealed that PVP-CUR nanoparticles markedly mitigated oxidative stress and reduced apoptosis in a HO-induced human retinal pigment epithelial cell line (ARPE-19) and promoted phenotypic polarization from M1 to M2 in an LPS-induced human microglial cell line (HMC3). Further studies demonstrated the prominent therapeutic effects of PVP-CUR nanoparticles on experimental autoimmune uveitis (EAU), which relieved clinical and pathological progression, improved perfusion and tomographic manifestations of retinal vessels, and reduced blood–retinal barrier (BRB) leakage; these effects may be mediated by mitigating oxidative stress and attenuating macrophage/microglia-elicited inflammation. Notably, treatment with PVP-CUR nanoparticles was shown to regulate metabolite alterations in EAU rats, providing novel insights into the underlying mechanisms involved. Additionally, the PVP-CUR nanoparticles showed great biocompatibility . In summary, our study revealed that PVP-CUR nanoparticles may serve as effective and safe nanodrugs for treating uveitis and other oxidative stress- and inflammation-related diseases.

中文翻译：

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具有免疫调节和代谢调节作用的聚乙烯吡咯烷酮-姜黄素纳米颗粒治疗实验性自身免疫性葡萄膜炎


葡萄膜炎包括一系列眼内炎症性疾病，其特征是不受控制的自身免疫反应和过度氧化应激，导致全球视力丧失。在本研究中，姜黄素（CUR）与聚乙烯吡咯烷酮（PVP）缀合形成PVP-CUR纳米颗粒，其溶解度显着提高，并具有出色的多重自由基清除能力。研究表明，PVP-CUR 纳米颗粒可显着减轻 H2O2 诱导的人视网膜色素上皮细胞系 (ARPE-19) 中的氧化应激并减少细胞凋亡，并促进 LPS 诱导的人小胶质细胞系 (HMC3) 中的表型极化从 M1 到 M2 。进一步的研究表明，PVP-CUR纳米颗粒对实验性自身免疫性葡萄膜炎（EAU）具有显着的治疗作用，可缓解临床和病理进展，改善视网膜血管的灌注和断层扫描表现，并减少血视网膜屏障（BRB）渗漏；这些作用可能是通过减轻氧化应激和减轻巨噬细胞/小胶质细胞引起的炎症来介导的。值得注意的是，PVP-CUR 纳米颗粒的治疗被证明可以调节 EAU 大鼠的代谢物改变，为所涉及的潜在机制提供了新的见解。此外，PVP-CUR纳米颗粒表现出良好的生物相容性。总之，我们的研究表明，PVP-CUR 纳米颗粒可以作为治疗葡萄膜炎和其他氧化应激和炎症相关疾病的有效且安全的纳米药物。