PDF(Pubmed)
Abstract：
UNASSIGNED: Patients afflicted with dry eye disease (DED) experience significant discomfort. The underlying cause of DED is the excessive accumulation of ROS on the ocular surface. Here, we investigated the nitrogen doped-graphene quantum dots (NGQDs), known for their ROS-scavenging capabilities, as a treatment for DED.
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.
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.
摘要：
患有干眼病(DED)的患者经历显著不适。DED的根本原因是ROS在眼表的过度积累。这里,我们研究了氮掺杂石墨烯量子点(NGQDs)，以其清除ROS的能力而闻名，作为DED的治疗。
■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。
■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。
