响应性两亲分子调控DNA组装体的构建及其性能研究

Self-assembly with building block DNA has become a reliable approach to construct DNA complex assemblies, which is the hotspot for cancer therapy and diagnosis in the field of physical chemistry, materials science and biomedicine science. In this project, we propose a novel method for the construction of DNA complex assemblies through the self-assembly of synthetically functional amphiphilic molecules or aggregates with DNA. External stimuli will be introduced to regulate the responsive assemblies and realize the application in cancer therapy. A series of smart hierarchical DNA assemblies with multifunctions and responsiveness will be prepared in the following systems including DNA/responsive catanionic vesicles, self-assembly of nucleic acid amphiphiles, DNA/responsive ionic liquid microgels, DNA/amphiphilic ligand modified inorganic nanomaterials. From the view of biophysical chemistry, we explore the construction methods, interactions and aggregation behaviors of the DNA assemblies, especially the effects on aggregates induced by the conformation, charges, rigidity of DNA, and the responsively functional building motif of amphiphilic molecules or aggregates. We will open up new avenues for the design of smart cargo delivery with controllable loading and release. The self-assembly methodology will expand its application in DNA nanotechnology and bioscience.

通过自组装技术构建DNA分子作为基本构筑基元的DNA复合组装体，以提高癌症治疗与诊断的效果，是目前物理化学、材料和生物医药交叉领域的研究热点。本项目以设计合成的功能性两亲分子与DNA进行组装的方式构建DNA复合组装体，通过功能性基团对外部环境的刺激响应调控其结构，进而实现该智能组装体在癌症治疗方面的应用。分别从DNA/响应性阴阳离子囊泡复合组装体、寡核苷酸两亲分子自组装结构、DNA/响应性离子液体微凝胶复合组装体、DNA/两亲分子修饰无机材料复合组装体四个方面构筑多功能响应性智能复合组装体。以生物物理化学视角，不仅围绕两亲分子与DNA组装形成新颖运载体的组装过程，分子间相互作用力和聚集方式进行基础研究，重点考察DNA构象、电荷和刚性以及不同两亲分子聚集体响应性功能基团的影响；而且建立一种新型的智能调控基因/药物包封与释放的组装方法，拓宽了自组装技术在构建功能性DNA纳米材料方面的应用。

DNA分子作为自组装领域的重要构筑基元，可以与两亲物质通过非共价或共价相互作用构筑DNA多功能复合材料，因此寻找结构新颖并能与DNA发生自组装的响应分子或两亲分子，深入研究DNA分子作为构筑基元形成的DNA-两亲分子多功能复合材料的特性与功能，可以极大丰富DNA复合组装体的类型与应用价值。因此本项目以设计合成的功能性两亲分子与DNA进行组装的方式构建DNA复合组装体，通过功能性基团对外部环境的刺激响应调控其结构，进而实现该智能组装体在生物、医药及荧光检测等方面的应用。分别从DNA/响应性阴阳离子囊泡复合组装体、DNA/两亲分子修饰无机材料复合组装体、DNA/响应性基元微凝胶、两亲纳米材料自组装构筑功能材料等四个方面进行探究。研究过程中不仅围绕两亲分子与DNA组装形成新颖组装体的组装过程、分子间相互作用力和聚集方式进行基础研究，重点考察DNA构象、电荷和刚性以及不同两亲分子聚集体响应性功能基团的影响，而且建立一种新型的智能调控基因/药物包封与释放的组装方法，有望拓宽自组装技术在构建功能性DNA纳米材料方面的应用。