仿生荧光DNA纳米管及其作为药物传递纳米载体的应用

Developing novel biocompatible, multifunctional drug delivery nanocarriers remains the key for the application of nanotechnology on drug delivery. DNA 3D nanostructures have the promising properties to be ideal targeted drug delivery nanocarriers. Several DNA 3D nanostuctures have recently been studied as different drug nanocarriers, but there are still issues to be addressed. In this project, we propose a novel biomimetic fluorescent DNA nanotube structure, which designed basing on the structure of green fluorescent protein (GFP) and the mechanism of the formation of its self-fluorescent chromophore. The excellent self-fluorescent property， comparing to organic fluorescent molecule labeled DNA 3D nanostructures, makes the biomimetic fluorescent DNA naotube have significant advantage in monitoring the process and mechanism of drug delivery. We will also study the application of this novel biomimetic fluorescent DNA nanotube as an universal multifunctional drug delivery nanocarrier for cancer treatment and gene therapy.

研究开发新型的、具有生物兼容性的、多功能的药物传递纳米载体对纳米技术在药物传递上的应用至关重要。DNA三维纳米结构具有成为理想药物传递纳米载体的优越特性。几种不同的DNA三维纳米结构也在最近被应用于药物传递的研究，但都还存在一些需要改进的地方。在本课题中，我们将参照绿色荧光蛋白的结构及其自生荧光生色基团的形成机理，设计、制备一种新型的仿生荧光DNA纳米管结构。其自生荧光的优异特性，使得仿生荧光DNA纳米管,相比于连接有机荧光分子的其它DNA三维纳米结构，在荧光示踪监控药物传递过程和机理方面具有独特的优势。我们也将探索这种新型的仿生荧光DNA纳米管作为普遍性的多功能药物传递纳米载体在癌症治疗和基因治疗中的应用前景。

在本课题中，我们参照绿色荧光蛋白（GFP）的结构及其自生荧光生色基团的形成机理，设计、制备出了能自生荧光的仿生DNA纳米管结构。并且进一步制备了利用癌细胞中过表达的microRNA来控制打开的荧光DNA纳米管结构，研究发现其可以顺利进入人体黑色素瘤细胞，在细胞中保持至少9个小时的结构完整，期间被黑色素瘤细胞中过度表达的miRNA-21逐渐打开管状结构。研究表明，仿生荧光DNA纳米管可以被用来作为具有生物兼容性的多功能的药物传递纳米载体，在生物医学研究中发挥重要作用。