基于Gd标记的磁性纳米粒子的合成及其在肿瘤靶向MRI中的应用

项目名称： 基于Gd标记的磁性纳米粒子的合成及其在肿瘤靶向MRI中的应用

项目编号： No.21271130

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 数理科学和化学

项目作者： 杨仕平

作者单位： 上海师范大学

项目金额： 80万元

中文摘要： 以氨基功能化的前躯体为原料，采用高温分解原位合成的方法，直接一步法得到氨基功能化的超顺磁磁性纳米粒子(如Fe3O4、FeCo、Fe)，再通过化学嫁接，引入不同链长的聚乙二醇(PEG)改善磁性纳米粒子的水溶性，同时调控T2模式磁性核与外围T1模式Gd之间的距离，运用化学修饰技术引入多羧酸配体与Gd3+的配位，得到双模式成像试剂材料；依据T2弛豫反演谱，分析结合水、束缚水、自由水的比例，分析T1和T2 的相互作用；分别以叶酸、RGD小分子多肽和前列腺特异性膜抗原PSMA受体高度表达的人口腔上皮癌细胞、人肺癌上皮细胞与前列腺癌细胞和小动物肿瘤模型为研究对象，依靠核磁共振成像手段，研究T1和T2双模式磁性粒子与肿瘤细胞的靶向成像作用，探索其在分子影像中的应用。工作的开展，不仅为磁性粒子的应用开发提供新思路，而且对于磁性粒子作为MRI试剂在医学和检测方面的作用，也具有现实的意义。

中文关键词： 靶向；磁性纳米粒子；核磁共振成像；肿瘤；

英文摘要： In this project, we will develop a multifunctional Gd-labeled superparamagnetic nanoparticles (Fe3O4, FeCo and Fe) for targeted dual mode T1- and T2-weighted MR imaging of tumors. Firstly, we utilized a thermal decomposition approach to synthesizing nanoparticles (Fe3O4, FeCo and Fe) which were capped by amino caproic acid. Then the nanoparticles were enabled covalent conjugation of polyethylene glycol (PEG) with different chain length, which can improve the water solubility of nanoparticles and adjust the distance between the central core and Gd3+ cation. Finally, Gd-DTPA (diethylenetriamine pentaacetic acid) complex and folic acid (FA) ligand or RGD peptide or PSMA antibody can further linked through chemical bonds onto the surface of nanoparticles.The targeting specificity of nanoparticles were evaluated by dual mode T1- and T2-weighted MR imaging in living cell U87MG cells (a human glioblastoma cell line with high avb3 integrin expression), Hela cells (A human cervical carcinoma cell line with FA receptor high expression )and PSMA antibody as tumor cell and it animal cancer model, respectively. The interaction and synergistic action of T1 and T2 mode was assessed by T2 invert relaxlation spectra in which the percentage of inner-sphere, secondary-sphere and bulk water was analyzed through area integral method

英文关键词： Targeting；Magnetic nanoparticles；Magnetic resonance imaging；Tumor；