【作者】 程昌明；

【导师】 古宏晨；

【作者基本信息】 上海交通大学 ， 应用化学， 2010， 博士

【摘要】 Fe₃O₄纳米材料以其独特的理化性质,被广泛的应用于生物医学领域,其中,磁共振成像是Fe₃O₄纳米材料的一个重要应用领域。在磁共振成像中,Fe₃O₄纳米颗粒可加速周边氢质子的横向弛豫,降低其磁共振信号,增强磁共振成像的图像对比度。Fe₃O₄纳米颗粒在磁共振成像中的对比增强效率通常用其水相分散液的横向弛豫率来表征,与材料的理化性质,如粒径,磁化强度等紧密相关,因此,实现材料的可控制备,对Fe₃O₄纳米材料在磁共振成像领域的应用具有重要意义。本文分别采用共沉淀法和多元醇法可控制备了水相分散稳定的Fe₃O₄纳米颗粒和纳米团簇,研究了影响产物性质的各种因素,考察了Fe₃O₄纳米颗粒/团簇在磁共振成像分子诊断和细胞成像中的应用效果。针对目前超顺磁成像对比剂制备过程中磁性纳米颗粒由于粒径小、磁性弱,难以进行分离、洗涤的问题,采用絮凝-再分散法制备了粒径5 nm左右的超顺磁性Fe₃O₄纳米颗粒,通过控制纳米颗粒在液相中的絮凝/分散状态,使得制备的Fe₃O₄纳米颗粒可以在较弱的磁场（200 mT）下实现快速分离和洗涤,经过再分散处理后的纳米颗粒具有很好的胶体稳定性。将制备的Fe₃O₄纳米颗粒与抗体耦联后用于肿瘤的分子诊断,取得了较好的结果。采用多元醇法制备了粒径为5³5 nm、单分散性好、磁化强度高、水相分散稳定的Fe₃O₄纳米颗粒,研究了多元醇和分散剂对颗粒性质的影响,结果表明多元醇分子的还原性和分散剂的结构对颗粒的形成和生长有重要影响。与商品化的超顺磁成像对比剂的横向弛豫率(<200 mM^-1s^-1)相比,多元醇法制备的Fe₃O₄纳米颗粒分散液具有更高的横向弛豫率(263 mM^-1s^-1),对质子横向弛豫的增强作用更明显,在磁共振成像领域具有很好的应用前景。采用多元醇法制备了一系列高磁性物质含量、表面亲水性的单分散Fe₃O₄纳米团簇,发现纳米团簇的形成是颗粒间斥力与颗粒/溶剂间表面张力共同作用的结果,研究了分散剂浓度和结构、反应物中水和前驱体的浓度、反应时间和温度等对于Fe₃O₄纳米团簇的影响,通过调节上述反应因素,可控制备了粒径从30 nm至450 nm、不同表面电性和结构的Fe₃O₄纳米团簇。以多元醇法制备的Fe₃O₄纳米团簇为材料,研究了Fe₃O₄纳米团簇粒径与质子横向弛豫率的关系,并且与理论预测结果作比较,结果表明粒径为60 nm左右的磁性纳米团簇对质子横向弛豫的增强作用最明显,其分散液中质子的横向弛豫率高达665 mM^-1s^-1,远高于商品化的超顺磁成像对比剂,也明显高于目前已报道的关于Fe₃O₄分散液的横向弛豫率数值(一般为400 mM^-1s^-1左右)。将制备的Fe₃O₄纳米团簇用于细胞标记和成像,证实Fe₃O₄纳米团簇可以显著的提高磁共振细胞成像的灵敏度,在细胞成像领域具有很好的应用前景。更多还原

【Abstract】 Magnetic iron oxide nanoparticles have been widely used as contrast agent in magnetic resonance imaging （MRI）, owing to their significant enhancement on the relaxation of protons. The efficiency of magnetic nanoparticles as contrast agent is usually quantified by the transverse relaxivity of the particles suspension. The transverse relaxivity is closely related with the physicochemical properties of magnetic nanoparticles, such as the size, surface property, magnetic property, and so on. The main challenge for the application of magnetic nanoparticles in this area is how to precisely tune the physicochemical properties of materials in a controllable way. In this dissertation, we have synthesized a series of magnetite nanoparticles and nanocrystal clusters with tunable properties and used them as contrast agents in MRI.We have developed a novel flocculation-redispersion method to synthesize superparamagnetic magnetite nanoparticles. By controlling the flocculation and release of magnetite nanoparticles in aqueous solution, the magnetite nanoparticles with size of ⁵ nm can be separated and purified by magnetic sedimentation conveniently. It greatly simplifies the post-processing in the production of the commercial superparamagtnetic contrast agent and avoids the tedious ultrafiltration process. After conjugation with monoclonal antibody, the magnetite nanoparticles have been used in the molecular diagnosis of tumor in mice in vivo and the desired result has been achieved. To improve the magnetization and uniformity of magnetite nanoparticles, we synthesized the magnetite nanoparticles with sizes ranging from 5³5 nm by a facile polyol process. The effects of the parameters on the properties of magnetite nanoparticles, have been studied carefully to obtain the efficient tools for tailoring the physicochemical properties of magnetite nanoparticles. The as-synthesized magnetite nanoparticles, with uniform size and high magnetization, possess the higher transverse relaxivity (263 mM^-1s^-1) than that of magnetite nanoparticles synthesized by traditional coprecipitation method (<200 mM^-1s^-1).We have developed a facile polyol process to synthesize the magnetite nanocrystal clusters with ultra-high magnetic content and hydrophilic surface. A new mechanism based on the interaction between the repulsion force and surface tension has been introduced to explain the formation of magnetic nanospheres in polyol process. By varying the reaction parameters to break the balance between the repulsion force and the surface tension, we obtained a series of magnetite nanospheres with sizes ranging from 30 to 450 nm. The structure and surface property of the nanospheres can be tuned tby the same way, too.The valuable exploration has been carried out on the relationship between the transverse relaxivity of magnetic nanospheres suspension and the diameter of the nanosphere. The transverse relaxivity of suspensions of magnetite nanospheres with size of 60 nm is 665 mM^-1s^-1, which is the highest value being published up to date. The synthesized magnetite nanopsheres with different coating materials have been used as cellular probe to visualize the cells in vitro and in vivo and the expected result has been proved by MRI.更多还原