UNASSIGNED: NGQDs were prepared by using citric acid and urea as precursors through hydrothermal method. The antioxidant abilities of NGQDs were evaluated through: scavenging the ROS both extracellular and intracellular, regulating the nuclear factor-erythroid 2-related factor (Nrf2) antioxidant pathway of human corneal epithelial cells (HCECs) and their transcription of inflammation related genes. Furthermore, NGQDs were modified by Arg-Gly-Asp-Ser (RGDS) peptides to obtain RGDS@NGQDs. In vivo, both the NGQDs and RGDS@NGQDs were suspended in 0.1% Pluronic F127 (w/v) and delivered as eye drops in the scopolamine hydrobromide-induced DED mouse model. Preclinical efficacy was compared to the healthy and DPBS treated DED mice.
UNASSIGNED: These NGQDs demonstrated pronounced antioxidant properties, efficiently neutralizing free radicals and activating the intracellular Nrf2 pathway. In vitro studies revealed that treatment of H2O2-exposed HCECs with NGQDs induced a preservation in cell viability. Additionally, there was a reduction in the transcription of inflammation-associated genes. To prolong the corneal residence time of NGQDs, they were further modified with RGDS peptides and suspended in 0.1% Pluronic F127 (w/v) to create RGDS@NGQDs F127 eye drops. RGDS@NGQDs exhibited superior intracellular antioxidant activity even at low concentrations (10 μg/mL). Subsequent in vivo studies revealed that RGDS@NGQDs F127 eye drops notably mitigated the symptoms of DED mouse model, primarily by reducing ocular ROS levels.
UNASSIGNED: Our findings underscore the enhanced antioxidant benefits achieved by modifying GQDs through nitrogen doping and RGDS peptide tethering. Importantly, in a mouse model, our novel eye drops formulation effectively ameliorated DED symptoms, thereby representing a novel therapeutic pathway for DED management.
■以柠檬酸和尿素为前体,通过水热法制备了NGQD。NGQDs的抗氧化能力通过:清除细胞外和细胞内的ROS,调节人角膜上皮细胞(HCECs)的核因子-红系2相关因子(Nrf2)抗氧化途径及其炎症相关基因的转录。此外,通过Arg-Gly-Asp-Ser(RGDS)肽修饰NGQD以获得RGDS@NGQD。在体内,将NGQDs和RGDS@NGQDs悬浮于0.1%PluronicF127(w/v)中,并在氢溴酸东莨菪碱诱导的DED小鼠模型中以滴眼液形式给药.将临床前功效与健康和DPBS处理的DED小鼠进行比较。
■这些NGQD表现出明显的抗氧化性能,有效中和自由基并激活细胞内Nrf2途径。体外研究表明,用NGQD处理暴露于H2O2的HCECs可诱导细胞活力的保留。此外,炎症相关基因的转录减少.延长NGQDs的角膜停留时间,用RGDS肽进一步修饰,并悬浮于0.1%PluronicF127(w/v)中,制成RGDS@NGQDsF127滴眼液.即使在低浓度(10μg/mL)下,RGDS@NGQD也表现出优异的细胞内抗氧化活性。随后的体内研究表明,RGDS@NGQDsF127滴眼液明显减轻了DED小鼠模型的症状,主要通过降低眼部ROS水平。
■我们的发现强调了通过氮掺杂和RGDS肽连接修饰GQDs所获得的增强的抗氧化益处。重要的是,在老鼠模型中,我们的新型滴眼液配方有效改善了DED症状,从而代表了DED管理的新治疗途径。