抗氧化剂分子修饰的巯基聚乙二醇金纳米颗粒的合成及其抗氧化应激机制研究

项目名称： 抗氧化剂分子修饰的巯基聚乙二醇金纳米颗粒的合成及其抗氧化应激机制研究

项目编号： No.31300697

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 生物科学

项目作者： 杜立波

作者单位： 中国科学院化学研究所

项目金额： 20万元

中文摘要： 随着金纳米颗粒逐步应用于临床诊断和药物输运等诸多领域，其作为载体的生物安全性就成为亟待解决的关键问题之一。目前普遍认为金纳米颗粒的毒性主要是由其造成的氧化应激损伤导致的，尽管这种氧化应激损伤可以通过表面巯基聚乙二醇化得以改善，但仍存在氧化应激损伤问题。因此，如何解决巯基聚乙二醇保护的金纳米颗粒所带来的毒性问题对于金纳米颗粒的生物学应用具有重要的现实意义。本研究在前期工作基础上，选取巯基二缩三乙二醇或巯基PEG5000作为配基，4.5nm金纳米颗粒作为纳米模型，拟通过合成不同活性的抗氧化剂分子，通过自组装方式制备抗氧化剂分子修饰的巯基聚乙二醇保护的金纳米颗粒，然后通过生物活性检测和毒性评估筛选出具有高效抑制氧化应激特性的金纳米颗粒，并对其抗氧化应激机制进行研究。基于上述研究，阐释提高巯基聚乙二醇保护的金纳米颗粒生物安全性的设计思路和方案，为巯基聚乙二醇保护的金纳米颗粒的生物学应用奠定基础。

中文关键词： 金纳米颗粒；抗氧化剂；自由基；氧化应激；细胞毒性

英文摘要： Gold nanoparticles (AuNPs) have become an indispensable tool in the development of clinical diagnostics and therapy. With the widely application of AuNPs, the cytotoxicity of AuNPs became one of the most important factors that should be primarily considered and evaluated, before making their application in practice. Account of previous studies demonstrated that the cytotoxicity of AuNPs is relevant with the generation of oxidative stress, which accompanied with the production of a variety of reactive oxygen species (ROS). Althouth the cytotoxicity of AuNPs can be relieved by surface functionalized with PEG, there still exist oxidative stress that influence its application in vivo.Therefore, it is of great significant to solve the cytotoxicity of AuNPs.Herein, based on our previous study, the antioxidants with high antioxidant activity was synthesized which were used as surface functionalization ligands. Subsequently, by self-assembly method, the gold nanoparticles (4.5 nm) were synthesized using the thiolated triethylene glycol/thiolated PEG5000 and the synthesized antioxidants as ligands. Moreover, the antioxidants with high antioxidant activity were selected by bioassay and toxicity assessment; the mechanism of oxidative stress were also studied, which might provide an ideal platform for the biological applica

英文关键词： gold nanoparticles；antioxidant；free radical；oxidative stress；cytotoxicity