DNA的功能化组装及其在肺癌检测和治疗中的应用研究

This project focuses on the assembly of DNA nanostructures and their multifunctionalization with signal probes such as fluorescence or electroactive molecules, biomolecules such as enzyme, antigen, antibody, DNA and variety of drugs. DNA nanostructure probes that have strong signals, high stability and good biocompatibility are developed by taking advantage of their ability to load more signal molecules and can be modified with variety of biomolecules on their specific site, and then, sensitive and simultaneous detection methods for lung cancer cell, lung cancer gene and lung cancer markers are developed; Multifunctional DNA nanostructures for target imaging and therapy of lung tumor are prepared by assembling of drugs, targeting agents and imaging compounds together; Study these DNA nanostructures' cytotoxicity and improve their stability, efficacity and specificity for lung tumors; Study its behavior in imaging and suppression of lung tumor by using lung cancer rabbit as model and realize their multifunctionality for diagnostics and therapeutics of lung cancer. The project is important for human health,life science and our creative ability in the field of bioanalytical chemistry.

本项目研究DNA纳米结构的功能化组装，发展DNA纳米结构组装体与荧光、电化学活性物质等信号分子及酶、抗原、抗体、DNA等生物大分子以及药物的组装方法。利用其对信号分子的高负载量以及可以在其不同位点同时精确组装几种不同生物分子的特性，构建信号强、稳定性和生物相容性好的DNA纳米结构生物探针，实现肺癌细胞、肺癌基因和多种肺癌肿瘤标志物的高效、灵敏检测；研究药物、靶向剂、成像剂在DNA纳米结构上的共同组装条件和方法，制备集靶向载药和成像示踪于一体的多功能DNA纳米组装体；研究该DNA纳米药物组装体的细胞毒性，探索提高其靶向给药的特异性、药效和稳定性的方法；利用肺癌裸鼠模型，研究该DNA纳米药物组装体在小鼠体内的活体成像以及对肺癌肿瘤的抑制功能，实现对肺癌细胞、肺癌基因的分子靶向、诊断、抑制与治疗。本研究对人类健康、学科交叉、生物科学的发展以及提高我们在生物分析化学领域的创新能力有重要意义。

本项目以研究DNA纳米结构的功能化组装为基础，发展DNA纳米结构组装体与荧光、电化学活性物质等信号分子及酶、DNA等生物大分子以及药物的组装方法。利用其对信号分子的高负载量以及可以在其不同位点同时精确组装几种不同生物分子的特性，构建信号强、稳定性和生物相容性好的DNA纳米结构生物探针，实现了多种与肺癌相关标志物如８-OHdG, DNA甲基化酶、miRNA、端粒酶、PARP-1酶的检测新方法；建立了基于荧光串扰校正和单个波长激发多组分同时检测三种肺癌相关的miRNA-155，miRNA-182 和miRNA-197；建立了肿瘤细胞内miRNA和端粒酶荧光成像可视化检测的新方法。这些癌症标志物的检测方法为肿瘤的临床早期诊断提供了新方法,有望在临床诊断上被广泛应用。