DNA在脂质体、纳米金表面杂交动力学的研究及生物应用

In this project, we immobilize DNA on a phospholipid surface, we choose to prepare DOPC liposomes containing 5% MPB-PE that can react with the 3’-end thiol-modified probe DNA to form a covalent linkage. Not only can the reaction be performed on DNA, more important, the method can also be used to conjugate thiol-modified DNAzyme and siRNA. The phospholipid surface is highly hydrated and should only have very weak interaction with immobilized DNA probes. We would like to systematically study and compare the hybridization rate of DNA on the liposome and gold nanoparticle surface. This will give us useful information on the hybridization rate of DNA on the surface of soft materials and hard materials. Based on the study, we will immobilize antisense DNA, DNAzyme and siRNA on phospholipid and AuNPs surface and investigate the ability of these nanoconjugates to regulate intracellular mRNA levels. This will give us useful information on the related gene downregulation rate of DNA on the surface of soft materials and hard materials.

在本项目中，申请人将巯基修饰的DNA点击到脂质体马来酰亚胺基团上的双键上。这一方法不仅适用于antisense DNA，也将适用于DNAzyme、siRNA等多种核酸体系中，因此是一种将核酸分子固定到脂质体上的简便方法。两性脂质体作为一种软材料，DNA在两性脂质体上的吸附作用力要明显弱于纳米金对DNA的吸附作用。我们将系统地研究DNA分子在两性脂质体、纳米金上的杂交动力学的差异。在细胞水平上进一步研究，与功能化的核酸-纳米金对比，将相应的核酸-两性脂质体，如巯基修饰的antisense DNA、DNAzyme、siRNA-两性脂质体应用于基因传递时，与细胞内靶RNA进行碱基配对结合，是否可更为有效地调控细胞内基因的表达。

在本项目中，申请人将巯基修饰的DNA点击到脂质体马来酰亚胺基团上的双键上。这是一种将核酸分子固定到脂质体上的简便方法。我们还将其拓展到脂质体与纳米材料的生物学效应上。项目在研三年，在Angew. Chem Int. Ed.，ACS Appl. Mater. Interfaces，Langmuir等发表第一或通讯文章（有标注）五篇。这些工作我们深入研究脂质在生物医学、分析、材料应用等提供了有益的指导。