Studies on the influence of one critical parameter （e.g., size）, targeting a specific disease, while keeping other factors unchanged, are important for improving understanding and application of the molecular design...Studies on the influence of one critical parameter （e.g., size）, targeting a specific disease, while keeping other factors unchanged, are important for improving understanding and application of the molecular design of biomedical nanomaterials. In this study, we used doxorubicin （Dox）-conjugated gold nanoparticles （GNPs） to investigate the effects of the size of the gold core （10, 20, or 60 nm） on the performance of their conjugates. We found that all three conjugates differed slightly in their physicochemical properties, facilitating a direct and accurate assessment of the size effects of GNP-Dox conjugates on their in vitro and in vivo performance. The cytological properties （the cell penetration rate and efficiency, as well as the cytotoxicity） and antitumor performance （the intratumoral penetration, treatment efficacy, and biodistribution） were highly correlated to the size of the inorganic core. Among all test groups, although the conjugate with a 60-nm gold core had the highest drug loading and release efficiency, the conjugate with a 10-nm gold core displayed the best antitumor efficacy toward the liver cancer models. This was because it showed the deepest tumor permeability and the highest tumor cell-killing ability of Dox transported by the relatively small GNPs. This study provides important evidence for better understanding the effect of size on in vitro and in vivo properties of potential therapeutic nanosystems and their structure design.展开更多
基金Scientific Research Project of Shanxi Provincial Health Commission(Grant No.2021040)Postgraduate Education Innovation Plan of Shanxi Provincial Department of Education(Grant No.2022Y710)Shanxi University of Traditional Chinese Medicine Postgraduate Innovation and Entrepreneurship Project(Grant No.2022CX007)。
文摘本研究使用网络药理学、分子对接结合实验验证探究当归补血汤在糖尿病视网膜病变(Diabetic retinopathy,DR)中的作用机制。从TCMSP、TCMID、Swiss Target Prediction数据库筛选当归补血汤活性成分及其靶点,通过Gene Cards、Dis Ge NET收集DR靶点,利用Venny 2.1获得二者交集靶点。使用Cytoscape构建“疾病-药物-成分-靶点”、蛋白互作(PPI)网络;DAVID数据库对关键靶点进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析;Auto Dock Vina对主要活性成分与关键靶点进行分子对接验证。最后,通过动物实验验证网络药理学结果。收集到当归补血汤与DR共同靶点84个。GO分析显示220个条目;KEGG富集分析得到113条信号通路。分子对接结果显示关键靶点与槲皮素、豆甾醇等有效成分均具有较好的对接活性。动物实验表明当归补血汤可改善DR大鼠视网膜组织形态,降低血糖,增加胰岛素分泌,降低DR大鼠视网膜组织VEGF、TNF-α蛋白表达水平、提高PI3K、Akt1表达水平(P<0.05,P<0.01)。当归补血汤治疗DR具有多活性成分、多靶点、多通路的特点,可通过调节TNF-α、VEGFA、PI3K、AKT等核心靶点,影响PI3K/AKT、TNF等信号通路发挥对DR的治疗作用。
文摘Studies on the influence of one critical parameter （e.g., size）, targeting a specific disease, while keeping other factors unchanged, are important for improving understanding and application of the molecular design of biomedical nanomaterials. In this study, we used doxorubicin （Dox）-conjugated gold nanoparticles （GNPs） to investigate the effects of the size of the gold core （10, 20, or 60 nm） on the performance of their conjugates. We found that all three conjugates differed slightly in their physicochemical properties, facilitating a direct and accurate assessment of the size effects of GNP-Dox conjugates on their in vitro and in vivo performance. The cytological properties （the cell penetration rate and efficiency, as well as the cytotoxicity） and antitumor performance （the intratumoral penetration, treatment efficacy, and biodistribution） were highly correlated to the size of the inorganic core. Among all test groups, although the conjugate with a 60-nm gold core had the highest drug loading and release efficiency, the conjugate with a 10-nm gold core displayed the best antitumor efficacy toward the liver cancer models. This was because it showed the deepest tumor permeability and the highest tumor cell-killing ability of Dox transported by the relatively small GNPs. This study provides important evidence for better understanding the effect of size on in vitro and in vivo properties of potential therapeutic nanosystems and their structure design.
