核酸载体修饰的硅纳米线阵列促进基因转染的研究

项目名称： 核酸载体修饰的硅纳米线阵列促进基因转染的研究

项目编号： No.21474072

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 数理科学和化学

项目作者： 王宏炜

作者单位： 苏州大学

项目金额： 90万元

中文摘要： 基因治疗是解决许多难治疗疾病的主要方向。选择生物相容性好的基因载体、高效负载和释放核酸物质及直接将其运输到细胞核内是开展基因治疗的关键。本项目提出利用高分子修饰的硅纳米线阵列，借助硅纳米线对细胞核的穿透性能及高分子物质对核酸结合与释放的调控，来提高基因转染效率且降低细胞毒性。本项目采用共价连接和表面引发原子转移自由基聚合技术（SI-ATRP），在不同形貌的硅纳米线阵列表面修饰聚乙烯亚胺、壳聚糖衍生物和聚甲基丙烯酸二甲氨乙酯等物质，构建一系列核酸载体分子修饰的硅纳米线阵列；研究材料表面对核酸的结合和释放，基因复合的控制及其在细胞内的释放过程；研究材料上蛋白质的结合与活性以及细胞的生长和转染效率，探讨高分子修饰的硅纳米线阵列影响基因转染效率的原因。该项目的研究可为进一步利用高分子修饰的纳米材料表面制备特异性的生物医用材料提供理论基础和实验依据，为新型生物智能材料的设计与制备提供必要的研究基础。

中文关键词： 基因转染；硅纳米线阵列；聚乙烯亚胺；聚甲基丙烯酸二甲氨乙酯；转染效率

英文摘要： Gene therapy is the main direction to solve many diseases difficult to cure. The key challenges in gene therapy is to identify a delivery vehicle (vector) that can effectively and safely carry a gene into the target cells, and most importantly, directly transport into the nucleus of the host cell. In the present project, in order to improve transfection efficiency and reduce cytotoxicity, we purposed the use of polymer-modified silicon nanowire arrays as an effectively delivery system, based on the penetration performance of the silicon nanowires on the nucleus and the regulation of polymeric substance on nucleic acid binding/release. A series of polymers, such as polyethylene imine (PEI), chitosan derivatives and polymethyl methacrylate dimethylaminoethyl methacrylate (PDMAEMA), are grafted by covalently-linking and surface initiated atom transfer radical polymerization technique (SI-ATRP) in silicon nanowire arrays with different morphologies, resulted in a series of polymer-modified silicon nanowire arrays. The effect of surface properties on nucleic acid binding/releasing, how to control gene recombination and its release process in the nucleus will be studied in this project. In order to investigate the reason why polymer-modified silicon nanowire arrays could affect gene transfection efficiency, the binding and activity of protein on the material surface, the cell growth and transfection efficiency will also be studied. This study will provide not only theoretical and experimental basis for the further use of polymer-modified nanomaterials surface as specific biomedical materials, but also the necessary foundation for the design and preparation of new biological intelligence material.

英文关键词： gene transfection;silicon nanowire arrays;polyethylene imine;poly(2-(dimethylamino ethyl)methacrylate);transfection efficiency