适配体靶向的纳米载体的钆基磁共振成像造影剂的构建研究

项目名称： 适配体靶向的纳米载体的钆基磁共振成像造影剂的构建研究

项目编号： No.21304106

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 数理科学和化学

项目作者： 刘敏

作者单位： 中国科学院苏州纳米技术与纳米仿生研究所

项目金额： 25万元

中文摘要： 为了提高钆基MRI造影剂的弛豫率及对肿瘤组织的造影成像能力，获得高灵敏、高特异性的肿瘤靶向磁共振造影剂，以实现癌症的早期诊断，本项目以造影剂弛豫理论为依据，设计和制备高弛豫率的基于适配体靶向的树形高分子-纳米棒载体的钆基MRI造影剂。在合成的低代树形高分子表面交联DTPA-Gd，满足与水分子的快速交换；将交联有DTPA-Gd的树形高分子组装到金纳米棒或ZnO纳米棒表面，可满足钆的有效负载量及机体对载体的尺寸要求；交联上HER2靶向的适配体，可实现HER2阳性的乳腺癌组织的富集。并系统地对构建的造影剂的MRI效果在细胞水平和活体水平上进行测试和评估。以求探索出构建高弛豫率基于靶向纳米载体的钆基MRI造影剂的一般规律和内在机理，为构建基于核酸适配体靶向不同癌组织的高灵敏MRI造影体系的普适方法提供理论依据和实验基础。

中文关键词： 磁共振成像；无机纳米粒子；大分子造影剂；可还原裂解；肿瘤靶向

英文摘要： MRI provides a three-dimensional and non-invasive imaging which has been widely used in cancer imaging. In order to enhance the detecting sensitivity and characterize the pathological abnormalities, contrast agents are used increasingly in diagnostic magnetic resonance imaging. In fact, it has been estimated that nearly 50% of all MR examinations already involve the use of contrast agents, with chelated gadolinium compounds being by far the most widely used. So far, the combination of nanotechnology and medical imaging contrast agents have profoundly promoted the development of the multifunctional device platforms. In order to obtain a new type of contrast agent with high sensitivity and targeting efficiency, in this project, the novel multifunctional gold and ZnO nanorods-based contrast agents simultaneously modified with gadolinium-conjugated dendrimer and aptamer against Her2 will be fabricated, which can deliver Gd-DTPA to the tumor area and achieve the early diagnosis of breast neoplasm. The Gd(Ⅲ) modified on the surface of dendrimer could facilitate the fast exchange between contrast agent-coordinated water molecules and water in the bulk solvent, and enhance the relaxivity. Then, we will investigate the nanoparticles' proper synthetic routes, surface modification and targeting ligands to obtain excelle

英文关键词： MRI；inorganic nanoparticle；macromolecular contrast agent；reductive cleavable；tumor targeted