基于深红/近红外两亲性BODIPY荧光纳米探针的设计、自组装及G-四链体DNA识别应用

G-quadruplex DNA, a new secondary DNA structure, plays important roles as regulatory elements in many biological processes, especially in regulating gene transcription and translation, and then affects cell proliferation and cancer progression. Detection of the quadruplex structures using probes will help to explore the distribution, function, and mechanism of G-quadruplexes in human cells, and may also provide new diagnostic and therapeutic approaches of cancer. While many small-molecule fluorescent probes for G-quadruplex DNA have been developed, there also still exist a lot of problems on selectivity, toxicity and biological compatibility. Recently, fluorescent nano-probes based on self-assembly of organic small molecules have been widely applied in detection of molecules in organisms, early detection of cancer and labeling drug delivery, due to their good selectivity, high sensitivity, better biological compatibility and real-time and in situ detection, etc. This project seeks to design and synthesize a series of far-red/near-infrared fluorescent nano-probes based on self-assembled amphiphilic BODIPY derivates. Tuning the ability of self-assembling and seletive recognition of nano-probes by rational design of their structures. Evaluation on the detection, regulation and intervention of G-quadruplex DNA at the level of cells of these recognition molecules was also investigated. This study will provide valuable data and theory foundation for the design of novel nano-probes for G-quadruplex DNA.

G-四链体DNA是一种特殊的核酸二级结构，涉及端粒维持、基因表达与调控、细胞的增殖和凋等过程。靶向G-四链体DNA识别分子的构建为理解该结构在人类基因中的分布、功能和机制奠定基础，也为解决抗肿瘤靶向性问题提供了一个新的契机。传统小分子荧光探针在识别G-四链体DNA过程中存在选择性不高、毒性大、靶向性及生物兼容性差等问题，限制了进一步应用。近年来，利用分子仿生的理念，通过分子自组装构筑具有特定性质的纳米材料在分子识别、癌细胞早期的发现和干预、药物传递示踪等方面展示出广阔的应用前景。为克服传统有机小分子探针的缺陷，本项目拟构建深红/近红外两亲性氟硼二吡咯荧光纳米探针，调节、优化分子结构以实现自组装行为的调控，提高特异性识别G-四链体DNA的能力。评价探针分子在细胞水平上的检测及调控和干预G-四链体DNA结构与功能的影响。为靶向G-四链体DNA的新型荧光纳米探针分子的构建提供新的思路和方法。