簇基MOFs纳米材料可控合成及药物缓控释研究

The NMOFs materials used in current drug delivery study have poor biodegradability, and release the active condiments too fast. The involved mechanisms are not clear yet. Addressing these issues, this project is proposed to design and synthesize a group of biodegradable metal-organic complexes having a structure similar to Si-O tetrahedrons, which could be further converted to Zeolite like MOFs aggregates by introducing a second ligands to replace those on the anchor sites. During the conversion procedure, amorphous or crystallized NMOFS could be obtained using a method of precipitation, co-precipitation method，reverse microemulsion method or surfactant template. The obtained NMOFs’ surface could be modified with a special “shell” to slow down drug releasing speed. Multiple drugs including the new anti-inflammatory drug Nervosine (I-VI), antibacterial medicine (Acacia and Quercetin) and anticancer drugs (Bai Xaio An) will be used as study platform to study the capacity and releasing capability of NMOFs in these three types of medicine. The interaction between drug molecules and the carrier principle structure would be explored. The synthesis methods of Zeolitie like NMOFs and their effects on drug capacity-release would be investigated. Combined with quantum chemistry theoretic simulation results the proposed work would be used to explain the structure-effect relationship, to predict experiment results and instruct synthesis practice. The purpose of this project is to provide a scientific basis for the development of novel drug carrier materials and further the integration of related regions in Chemistry, Materials, Biology and Pharmacy.

针对目前MOFs材料用于药物缓控释研究时存在的生物降解性差, 释药速度过快及机理不明等缺点，本项目拟设计可降解活性配体与金属离子模拟硅氧四面体，进一步由第二配体取代占位点定向可控合成类沸石型MOFs聚合物；利用纳米沉淀法、共沉淀法、反向微乳法、表面活性剂模板法等调控得到无定型或晶态NMOFs， 并对其表面进行“包壳”修饰以解决释药速度过快的问题； 以新型抗炎药吡咯里西啶类生物碱及其异构体(6种)、抑菌药金合欢醇和槲皮素、 抗癌药白消安为负载-控释观测平台，研究NMOFs对这三种药的负载及溶液中的释放能力， 探讨药物分子与主体骨架之间的相互作用方式，总结簇基类沸石型NMOFs合成规律及其对药物负载-控释的影响规律，并通过量子化学计算理论模拟，达到解释构效关系并预测实验结果，指导合成的目的。项目的实施为开发新型药物载体材料提供科学依据和实验基础，促进化学、材料、生物与药学等多学科的交叉融合。

金属有机骨架材料（MOFs）具有可设计易调控的有序结构、高孔隙率和大比表面积等特点，在生物活性、药物缓释、发光和吸附等方面有广阔的前景。本研究由性能为导向，开展了具有多功能的MOFs材料的定向合成研究。系统选用刚性三唑类、吡嗪类、咪唑类、三苯环三羧酸、以及柔性氮杂环(吡啶、吡嗪)羧基、柔性二羧酸类6大类配体，通过浓度-温度因素、辅助基元、pH值、溶剂诱导等方面控制合成了一系列MOFs材料，分别进行了生物活性、药物缓释、荧光性能以及吸附性能的研究，总结各类功能MOFs的合成及结构特点，得到功能-结构之间的对应关系，最终达到解释构效关系并预测实验结果，指导合成的目的。项目的实施为开发新型多功能MOFs材料提供科学依据和实验基础，促进化学、材料、生物与药学等多学科的交叉融合。