基于“点击”SERS光谱的DNA逻辑门在肿瘤细胞智能识别与精准成像中的应用

More precise identification of the nature of single tumor cells could be achieved by molecular profiling the expression levels of multiple membrane receptors, thus enabling more accurate cancer diagnosis and effective (intervention) therapy. On the basis of our previous researches involved in SERS and logic gates, and also, considering the single narrow band-based (1-2 nm) SERS scattering properties including high sensitivity, hyper spectral resolution and none optical interference, this project aims to synthesize and screen noble metal nanoparticles with high SERS effect and stability, a series of alkyne SERS reporters with high differential scattering section and band shift-tunable (1800-2600 cm-1) triple bond, and further allow the controllable splicing of SERS-active nanoparticles depending on several DNA computational tools, such as aptamer recognizing based method, strand displacement reaction, enzyme digestion and etc. to develop a ‘Click’ SERS logic gate based on a completely new readout form so called dynamic combinatorial spectroscopy. Finally, special auto-reading software will be developed to recognize and quantify the ‘click’ SERS signals. The success of this strategy will demonstrate the potential of this DNA logic gate in facilitating the intelligent response and synchronous detection of multiple membrane receptors of single tumor cells. This project is to provide a research platform for intelligent identification and accurate imaging of tumor cells.

单细胞水平定性/定量描述肿瘤细胞表面多种受体分子是开展肿瘤精确诊断与有效治疗的关键。本项目拟在课题组前期表面增强拉曼光谱（surface-enhanced Raman spectroscopy, SERS）与逻辑门工作基础上，发挥炔烃类SERS信号分子碳碳三键高灵敏、高光谱分辨、无光干扰的“窄带（1-2 nm）单峰”特性，制备和筛选高增强活性和高稳定的贵金属纳米颗粒，设计与合成高微分散射截面、三键SERS谱带在1800-2600 cm-1区间可调谐的系列标记分子，借助适配体识别、链置换反应及酶切等DNA“计算工具”诱导SERS活性纳米粒子可控拼接，构建基于动态组合输出全新模式——“点击”SERS光谱的DNA逻辑门，进而开发针对此光谱信号输出的定性/定量自动读取软件，实现单个肿瘤细胞中多种膜蛋白受体的种类和含量的智能响应和同步检测，为肿瘤细胞的智能识别与精准成像提供一种新型的研究平台。

本项目除了系统开展包括点击SERS在内的各种叁键SERS编码输出及其在细胞成像和胞内外检测中的应用以外，项目组在SERS基底制备和生物检测、光热纳米材料的合成及其抗肿瘤和杀菌应用等研究上都进行了拓展。共发表SCI论文23篇，中文核心论文2篇，其中影响因子大于5的SCI论文17篇，其中Journal of the American Chemical Society 1篇，Angewandte Chemie International Edition 1篇，Chemical Communications 1篇，Applied Materials Today 2篇，Chemical Engineering Journal 1篇，Small 1篇，Nanoscale 2篇，Analytical Chemistry 4篇等等。在本项目的支持下，课题组“单个聚合物纳米粒子上的叁键编码及其用于多重SRS成像”的原创工作继点击SERS发表于JACS之后再次获得顶级化学类期刊Angewandte Chemie International Edition的青睐，远远超出项目申请时的预期研究成果。在研究生培养上，共计培养博士研究生和硕士研究生18名。