本项目的立论以"杆形"病毒的超感染性为启示，以超分子组装调控微载体拓扑形貌为依据，采用基于环糊精的超分子组装技术，利用PEG链段与α-CD主客体嵌套对"刚柔"嵌段的调节实现对载体拓扑形貌的调控，制备具有不同拓扑结构的非病毒基因载体；从细胞和活体水平，深入研究载体拓扑结构对于基因载体体内生物分布、胞内运转和转染的基本规律；并进一步结合仿生智能聚合物的设计，利用双硒仿生聚合物及pH敏感PEG包被技术，制备杆形结构和刺激响应功能协同作用的多功能基因载体，为突破高效安全的基因功能微载体的技术瓶颈寻求切实可行的途径。

Rod-like virus show especially high infection in host cells. Following the inspiration, a new strategy will be explored to develop non-viral gene vector via the combination of the biomimic viral topology and stimuli-responsive polymer. α-CDs should exclusively thread on the PEG blocks in PEI-Se-Se-PEG copolymers via supramolecular assembly. The resulting complexes have both rigid block (PEG-α -CD) and coil block (protonated PEI). By varying the rigid block fraction, the topology of gene polyplexes will be regulated. The effect of shape on bio-distribution, cell uptake and gene transfection will be explored by cell culture and in vivo experiment. The usage of biomimic PEI-Se-Se-PEG and pH-sensitive PEGylation will facilitate gene release at target site. The combination strategy of rod-like shape and stimuli-responsive function will provide a facile approach to construct safe and efficient gene vector.