基于超小Fe@Fe3O4纳米粒子的T1磁共振成像研究

The development and application of nanoparticles based T1 weighted magnetic resonance imaging agent is currently a hot topic in research and industry. In order to investigate the T1 magnetic resonance imaging affected by the particles size and obtain the ultra-small Fe@Fe3O4 nanoparticles with best T1 magnetic resonance imaging effect, the Fe@Fe3O4 nanoparticles were synthesized firstly by thermal decomposition of different iron precursor. Then, it was modified by small molecule compounds or polymers with different groups and charges using chemical modification method (ligand exchange and covalently bonded), and the cell phagocytosis effect of ultra-small Fe@Fe3O4 nanoparticles with different surface ligand was investigated after that. At last, the T1 magnetic resonance imaging effect, tissue distribution and pharmacokinetics of ultra-small Fe@Fe3O4 nanoparticles with different surface ligand were studied based on the small animal model for human lung tumor which is highly expressed by the integrin receptor. To carry out this work can not only provide new ideas in the development of magnetic particles application, also play a positive role in frontier exploration for application and development of related materials on the translational medical application.

具有T1磁共振成像效果的纳米造影剂的开发与应用是当前学科研究和产业界的热点。采用不同铁的前躯体，利用高温热解法，合成不同粒径的Fe@Fe3O4纳米粒子，探索其粒径大小和T1磁共振成像效果之间的关系，获得具有优良T1磁共振成像效果的超小Fe@Fe3O4的纳米粒子。借助配位取代和共价键合等化学修饰方法，在超小Fe@Fe3O4的纳米粒子表面修饰具有不同基团与电荷的小分子化合物或高分子聚合物，探讨肿瘤细胞对具有不同表面修饰的Fe@Fe3O4纳米粒子的吞噬效果；以整合素受体高度表达的人肺癌上皮细胞小动物肿瘤模型为研究对象，研究不同表面修饰的Fe@Fe3O4纳米粒子在体内的T1磁共振成像效果、生物分布及代谢动力学。该工作的开展，不仅对磁性粒子的应用开发提供新思路，而且对相关材料在“医工转化”的应用与开发进行前沿性探索，也有着积极的现实作用。

本项目围绕超小Fe@Fe3O4磁性纳米粒子，开展了三个方面的研究工作：将Fe@Fe3O4磁性纳米粒子的核磁成像的功能与肿瘤治疗有机结合起来，开展了核磁共振成像引导的肿瘤治疗方面的研究，实时评价肿瘤治疗的效果；将研究对象延伸到超小Fe3O4磁性纳米粒子，对其修饰不同表面配体、染料分子，与金属有机框架化合物ZIF-8、Cu2O等纳米材料复合，开展其核磁共振成像以及双模态成像，推动肿瘤精确诊断的发展；将Fe@Fe3O4磁性纳米粒子在肿瘤诊断或者诊疗方面的研究扩展到肿瘤协同（光热）治疗方面的工作。解决肿瘤治疗中有效性，耐药性等问题。本工作的开展，不仅为Fe@Fe3O4磁性纳米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也具有现实的意义。