通过纳米递送系统的功能性组装协调siRNA的负载、输运与释放

项目名称： 通过纳米递送系统的功能性组装协调siRNA的负载、输运与释放

项目编号： No.31271073

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 董岸杰

作者单位： 天津大学

项目金额： 85万元

中文摘要： siRNA的体内靶向递送是临床应用的主要瓶颈，也是纳米药物递送领域研究的热点。siRNA的递送过程包括：纳米载体负载结构刚性的siRNA，经血液循环和细胞间质输运到靶细胞，靶细胞胞吞、内涵体逃逸并释放siRNA到细胞质内。这一复杂的递送过程需要纳米递送系统协调发挥siRNA负载、输运和释放功能，而这些功能的协调发挥取决于递送系统的多功能组装和结构控制。本项目以"柔性结构的阳离子聚合物复合纳米粒化的siRNA"为基本思路，结合聚乙二醇的保护作用，利用内涵体低pH和细胞质内谷胱甘肽浓度高的特点，进行纳米递送系统的功能性组装；研究阳离子聚合物与siRNA的相互作用、递送系统与组织及细胞的相互作用；研究阳离子聚合物链柔性、电荷密度、亲疏水性、氢键作用和纳米递送系统的可变形性等结构因素对递送系统功能性的影响，探讨协调发挥siRNA负载、输运和释放功能的有效途径，为siRNA递送系统开发应用提供指导。

中文关键词： siRNA；纳米载体；靶向递送；构效关系；两亲性聚合物

英文摘要： The systemic delivery of siRNA to its target remains the biggest hurdle to clinical translation, which is also the focus issue in nanotechnology field for drug delivery. siRNA loaded nanocarriers should transport siRNA to the target cells by crossing the vascular endothelial barriers and extracellular matrixes, then be uptaken by the target cells, escape from the endosomes and release siRNA to the cytosol. In order to perform the functions of siRNA loading, delivery and release in sequence and controlledly, the nanocarriers should be multifunctional assembled and controlled in structure. For the functional assembly of the siRNA delivery systems, this project plans to assemble flexible polycations with siRNA conjugated nanoparticles by utilising the properties of the lower pH in the endosomes and the higher concentration of glutathione in the cytoplasm. This project will study the interactions of the polycations with siRNA, the nanocarriers with the tissue and cells.The effects on the delivery systems of the chain flexibility, hydrophobicity, hydrogen bonding interaction of the polycations and the deformable properties of the nanocarriers will be studied. By this work, we try to find out the efficient route to adjust the siRNA loading, delivery and release, which can provide information for the development and ap

英文关键词： siRNA；nanocarriers；targeted delivery；structure-function relationship；amphiphilic polymer