基于金属表面活性剂的细乳液聚合法制备高效多功能核磁共振成像造影剂的研究

Magnetic resonance imaging (MRI) exhibits great values in diagnose of serious diseases in their early stage. The precise and accuracy of MRI is dictated by the sensitivity and targeting effect of MRI contrast agents. In this project, the concept of metallosurfactant is introduced into the preparation of MRI contrast agents. By utilizing metallosurfactant mediated miniemulsion polymerization, it is possible to obtain multi-modal and multi-functional MRI contrast agents. With rational molecule design, Gadolinium(III) complexes are chemically modified into metallosurfactants, meanwhile, the polymers, monomers and cosurfactants are screened and the conditions of miniemulsion polymerization are controlled, the sizes of obtained metallocolloids and densities of Gadolinium complexes on the surface of colloids are thus optimized. The rotation correlation times of Gadolinium complexes will be lengthened due to the slow tumbling rates of these metallocolloids, the sensitivity of these MRI contrast agents will thus be greatly enhanced. The miniemulsion polymerization system can also accommodate other contents with different kind of functionalities, such as fluorescence imaging, T2 MRI imaging and thermal therapy, which provides a facial way to generate multi-modal and multi-functional medical probes for clinical diagnose. By integrating polymer synthesis and medical chemistry through the concept of metallosurfactant, this project will provide new inspiration for developing new medical probes for clinical use.

核磁共振成像（MRI）在重大疾病早期诊断中有着重要应用价值。MRI诊断的精准程度取决于所采用的造影剂的灵敏度和靶向作用。本项研究将金属表面活性剂的理念引入到MRI领域中，结合细乳液聚合方法，制备多模式多功能的MRI造影剂。本项目采用合理的分子设计，以钆配合物为母体，通过适当的化学修饰手段使其具备表面活性。同时选择合适的聚合单体或聚合物、共表面活性剂以及细乳液聚合/分散反应条件，调控所得功能性高分子纳米粒子的大小以及钆金属离子的分布密度。利用高分子纳米粒子在溶液中慢翻转的特性，增加钆配合物的自旋相关时间，从而提高其作为MRI造影剂的灵敏度。此外，利用细乳液分散体系的包容性，引入带有荧光成像功能、T2成像功能或者具有热疗功能的纳米粒子，可以方便地制备多模式多功能的探针，用于临床诊断。本项研究将高分子合成化学与医药化学通过金属表面活性剂而有机地结合在一起，为新型临床探针的制备开辟一条新的思路。

核磁共振成像（MRI）在重大疾病早期诊断中有着重要应用价值。MRI 诊断的精准程度取决于所采用的造影剂的灵敏度和靶向作用。本项研究将金属表面活性剂的理念引入到MRI 领域中，结合细乳液聚合、分子自组装等方法，制备多模式多功能的MRI 造影剂。本项目采用合理的分子设计，以钆配合物为母体，通过引入适当长度的烷基链或者引入季铵盐等手段使其具备表面活性。同时选择合适的聚合单体、共表面活性剂以及细乳液聚合/分散反应条件，调控所得功能性高分子纳米粒子的大小以及钆金属离子的分布密度；通过选择合适的聚合物、纳米粒子等实现可控自组装。利用所得高分子复合纳米粒子在溶液中慢翻转的特性，增加钆配合物的自旋相关时间，从而提高其作为MRI 造影剂的灵敏度。利用分子自组装体系的包容性，还引入了带有荧光成像功能的纳米粒子，具有EPR被动靶向效应的纳米粒子等，方便地获得了多模式多功能的探针，用于临床诊断。此外，结合本研究组的相关项目，探索了新型抗肿瘤药物的设计合成，高水合常数MRI造影剂的设计合成等，以期获得集诊断与治疗于一体的新型MRI造影剂。本项研究将高分子合成化学与医药化学通过金属表面活性剂而有机地结合在一起，为新型临床探针的制备开辟了一条新的思路。