多模态光学响应无机纳米四棱锥的构筑及癌症标志物的胞内多重定量检测

This project will carry out experimental and theoretical study on controllable self-assembly, optical properties regulation and intracellular multiple detection applications of inorganic rectangular nanopyramid superstructures. Due to their unique three-dimensional structures and rich encoding features, rectangular nanopyramid can be an excellent model for the construction of multiple optical effects, coupling mechanisms exploration and the implementation of multiple detection. Following the controllable constructions and optical model building of rectangular nanopyramid of multicomponent and multiconfiguration, this project will carry out the study of surface-enhanced raman scattering, chirality enhancement and luminescence effects. This project aims at exploration of plasmon-plasmon coupling and plasmon-exciton coupling with short-term or long-term, the energy transfer and environment-related mechanism of upconversion luminescence, chirality enhancement mechanism, and the inherent law betweeen the structure, configuration and multiple optical effects. Meanwhile, this project will also carry out the interation study between the rectangular nanopyramid and biological molecules, through the multiple recognition probes from the nucleic acid framework of nanoassemblies. This project aims to establish intracellular multiple analysis method with ultrasensitivity for biomarkers related to a certain cancer, and develop new methods for accurate early diagnosis of malignant tumors. This project may make significant progresses in the construction methodology for complex inorganic nanoassemblies, structure-activity relationship, and developing new methods for accurate early diagnosis of cancers.

本项目拟针对无机纳米四棱锥超结构的构筑、构型与光学性质调控及胞内多重检测应用开展试验与理论研究工作。纳米四棱锥，由于其独特的三维结构和丰富的可编码特性，有利于多重光学效应及其耦合机制的研究和多重检测的实施。本项目拟基于可控自组装技术，构筑多组分、多种构型的纳米四棱锥；结合光学模型的构建，研究表面增强拉曼、手性增强和荧光效应，探索短程和长程的等离子-等离子耦合、等离子-激子耦合、上转换发光的能量转移机理及与外场关联机制、手性增强机制，解析结构、构型与多重光学响应的内在规律；基于纳米四棱锥核酸骨架的多重识别探针，研究纳米四棱锥与细胞内生物分子的相互作用，建立针对某一种恶性肿瘤相关的癌症标志物的超灵敏、多重的胞内原位分析，发展恶性肿瘤的早期精准诊断的新方法。通过项目实施，有望在复杂无机纳米组装结构构筑方法学、构效机制及恶性肿瘤的早期精准诊断新方法等方面取得重要进展，获得原创性科研成果。

纳米材料组装体，由于其组装基元的集体协同效应，具有独特的光、电、磁、力学等优异性；可控调节组装基元的粒子数目、种类、形貌、粒子间距及其组装模式与框架，可以呈现出各种组装形态以及多重信号响应，在生物分析、疾病诊断、医学成像、光子器件等具有广泛的应用。本项目基于纳米粒子定向功能化修饰技术，构筑了Au20-UCNP20、Au20-Cu9S5-Ag2S-UCNP20、Au20-Au30-UCNP、Au30-Au15-Au15等多组分、多种构型的纳米四面体、内嵌纳米四面体组装结构8种，发展了可控、高效纳米四面体自组装技术4种；构建了4组光学模型和4种电磁场模型，揭示了等离子-等离子耦合、等离子-激子耦合、上转换发光的能量转移机理及与外场关联机制、手性增强机制，解析了结构、构型与多重光学响应的内在规律。基于纳米四面体核酸骨架的多重识别探针，揭示了不同种类纳米四面体与细胞内生物分子的相互作用，建立了多重microRNA、端粒酶、表面糖蛋白、细胞凋亡蛋白标志物Caspase-3/7等重要疾病标志物的早期、超灵敏胞内原位定量检测方法，microRNA21检测范围为0.073-43.64fmol/10μgRNA, 胞内检测限为0.03fmol/10μgRNA（CD信号），microRNA-203b的胞内检测限为 0.09fmol/10µgRNA（荧光信号），端粒酶活性的胞内检测限为7.6×10-16IU（拉曼信号），表面糖蛋白的胞内检测限为0.53pg/mL（拉曼信号）。发展了恶性肿瘤等重大疾病的早期精准诊断的新方法2种，为复杂无机纳米组装结构构筑方法学、构效机制及恶性肿瘤的早期精准诊断新方法等方面提供了有力的基础支撑。发表高水平研究论文10篇，授权国家发明专利5项，培养研究生5名。