共轭聚合物-DNA自组装体系的制备、光学性质表征、及药物的控制性释放

项目名称： 共轭聚合物-DNA自组装体系的制备、光学性质表征、及药物的控制性释放

项目编号： No.51503096

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 一般工业技术

项目作者： 田雷蕾

作者单位： 南方科技大学

项目金额： 20万元

中文摘要： 基于共轭聚合物的荧光纳米粒子是生物成像纳米材料家族中的新成员，由于其生物相容性良好、毒性低、光捕获能力强、光稳定性好等特点，受到了越来越多的关注。目前，这类有机荧光纳米颗粒的最高荧光量子效率已经达到了和无机荧光量子点相同的水平;但相对于无机纳米粒子，有机纳米粒子在药物输送、疾病诊疗方面的开发研究还很欠缺。本课题拟将共轭聚合物引入DNA纳米结构中，开发具有药物可控释放功能的荧光纳米材料。在现代纳米技术中，DNA不仅仅是一种生物大分子，更是一种最智能、最特异、最可控的新型材料。研究表明恒温滚环扩增反应（RCA）制备的高浓度、高分子量的DNA更易形成热力学稳定的纳米结构。因此本课题拟利用RCA方法制备DNA，并发展超分子方法制备共轭聚合物和DNA的自组装体系，获得具有高荧光量子效率和优良稳定性的纳米颗粒；设计特定的DNA序列，赋予荧光纳米材料对癌症细胞特异选择性和可控性的药物释放功能。

中文关键词： 共轭聚合物；荧光纳米粒子；超分子自组装；生物医药应用；荧光共振能量转移

英文摘要： Fluorescent nanoparticles based on π-conjugated polymers (CPs) have been developed in recent years. Owing to the highly delocalized π-conjugated backbones, CPs show superiority over small organic dyes in terms of higher absorption, better photostability, larger Stokes shift, and stronger intermolecular interactions. Recently, as one of the most important bio-imaging materials, CP nanoparticles have been demonstrated comparable to inorganic quantum dots in fluorescence quantum yields. However, in the field of stimuli-responsive drug delivery, very little work has been done on CP nanoparticles. Compared with synthetic polymers, DNA exhibits many unique properties, including its biological function, biocompatibility, and molecular recognition capacity. Thus in this project we plan to design and develop a kind of novel nanoparticles based on conjugated polymers and DNAs, which will show multiple functions of selective cancer cell recognition, bio-imaging, and stimuli-responsive drug delivery. First, several conjugated polymers showing near-IR fluorescence or photoacoustic effect will be designed and synthesized, in order to realize deep tissue penetration. Condensed DNA/RNA nanostructures are produced from rolling circle amplifications (RCAs). Next, different supramolecular strategies are developed to fabricate the self-assembling systems of CPs and DNAs; and the most stable and highly fluorescent nanoparticles will be screened for the further modifications. The built-in multi-functional sequences can be readily induced in the DNA/RNA building blocks through designing the templates for RCA reactions. We will introduce the gene drug sequence (for example, antisense oligonucleotides, SiRNAs, or ribozymes), the cancer cell-targeting aptamer sequence for selective cancer cell recognition, and the recognition sequence for endonuclease enzymes, into the DNA/RNA building blocks. As parts of the nanoparticles, the “protected” enzyme nanocapsules will be included, in which the endonuclease is encapsulated into a positively charged thin polymeric shell cross-linked by acid-degradable or reducing-degradable cross-linkers. Once the nanoparticles are delivered to cells, the endonuclease enzyme will be “activated” and cut DNA/RNA building blocks to a high volume of gene drugs.

英文关键词： Conjugated polymer;Fluorescent nanoparticle;Supramolecular self-assembly;Biomedical application;Fluorescence resonance energy transfer