离子型金属-有机框架材料的设计、制备及其多模态诊疗机制研究

The clinical therapy for cancer is limited by the single diagnostic/therapeutic mode and the disconnection between them. Thus, the multimodal theranostic materials which include imaging compounds for tumor diagnosis and therapeutic agents for therapy may improve survival rate. It is suggested that Ionic Metal-Organic Frameworks (IMOFs) can be used as ideal multimodal theranostic materials aiming at tumor tissues, due to their diverse chemical compositions, designable porous structures, modifiable functionality and loadable capacity of ionic molecules. The preparation approaches of theranostic IMOFs can be proposed by taking consideration of the properties of compositions, especially magnetic metal ions as contrast agents for magnetic resonance imaging (MRI) and therapeutic compounds for cancer treatment. The empty interior porositites/channels of IMOFs provide ideal sites for capacity of theranostic agents. The effects of structure and electrical property of frameworks on the loading dynamics will be discussed and the synthesis conditions of desired frameworks will be attempted and optimized, with the aim to establish the preparation methodology of multimodal theranostic IMOFs. Our research focuses on the controlled release of guest molecules which are related with the organic ligands. We are aiming to clarify the influence of geometry features of pores on the release processing of guest molecules, and further investigate the relationship between the structure of MOFs and the property of multimodal theranostic materials. This study will give a deeper insight to design and fabricate IMOFs that provide a platform for multimodal diagnosis and therapy, and make IMOFs possible to be used as excellent theranostic materials in clinic applications.

单一的诊断、治疗方式以及两者间的脱节限制了癌症治疗的发展，多模态诊疗（即基于单一材料实现多种成像技术和治疗手段并行）可望解决以上问题，提高诊疗效果。离子型金属-有机框架材料不但具有化学组分多样性、结构可设计性和材料可修饰性等特点，而且材料孔洞对离子型客体分子具有可装载性，因此，离子型金属-有机框架材料是一种理想的多模态诊疗材料。本项目拟通过选用具有成像功能的金属离子和治疗效果的有机分子，探索自带诊疗性能的离子型金属-有机框架材料的合成条件；利用材料内部孔洞对客体分子的可装载性，研究其结构、电性对多种诊疗剂装载动力学的影响，完善具有多模态诊疗效果的离子型金属-有机框架材料的制备方法学；通过材料中官能团的改变考察材料对多种诊疗剂释放的作用，研究其与客体分子释放以及病变组织诊断、治疗的构效关系。项目研究将为具有多模态诊疗功能的离子型金属-有机框架材料的设计、制备及其医学应用奠定理论和实验基础。

本项目基于金属-有机框架材料的化学组分多样性、结构可设计性、孔道可装载性等特点，开展了离子型金属-有机框架材料的合成及其多模态诊疗性能的研究。通过具有诊断或治疗功能的化学组分，合成具有诊疗性能的离子型金属-有机框架材料，完善了离子型金属-有机框架材料的制备方法学；利用框架材料离子性和孔道空间，实现多种诊疗剂的装载，构建多模态诊疗材料体系；研究材料对多种客体分子的装载动力学，阐明离子型框架材料与诊疗剂装载的构效关系；分析孔道内诊疗剂的释放行为，探明框架材料对客体释放的作用规律，达到材料体系在肿瘤环境多模态诊疗目的。项目研究为具有多模态诊疗功能的离子型金属-有机框架材料的设计、制备及其医学应用奠定理论和实验基础。在本项目资助下，发表SCI论文11篇，申请国家发明专利6项，培养硕士研究生5名。