新型多功能贵金属纳米探针与microRNA 高效检测新方法研究

Characters)：MicroRNAs (miRNAs) play key regulatory roles in a diverse range of biological processes, including cell development, differentiation, metabolism and apoptosis. Especially, distinct miRNA expression patterns are associated with various canceres. This work designs various multifunctional noble mental nanoprobes with unique optical or electrochemical properties by controllable synthsis of noble mental nanoparties, and subsequent rational assembly and modification of diverse biomolecules on the nanoparticles surfaces. The obtained multifunctional noble mental nanoprobes are used to specifically recognize the target miRNA in circular blood or intracelluar miRNA by mulitiple measurement techniques.The controllable synthesis of noble mental nanoparticle such as gold naorod, cluster, silver nanocluster or composite nanoparitcle with unique optical or electrochemical properties will be investigated. The influnce of the shape,size, composition to the properties of the nanoparticles will be studied. Combining the surface modified techniques and signal amplification strategies with effective recognition capabiltiy of biomolecular, multifunctional noble mental nanoprobes for effective miRNA detection will be designed.Using the miRNA in circular blood or cancer intracelluar as model, effective miRNA detection strategies will be developed. In addition, the influence of the corresponding cancer drug,interference RNA and other factors to the expression patterns of miRNA will be studied. Therefore, the proposed work possess promising application in exploration of miRNA biofunction, development of useful diagnostic and prognostic cancer markers and exploitation of novel cancer drugs.

)：MicroRNA（miRNA）对生物体中一系列生命过程起着重要的调控作用，miRNA 的表达模式与人类的重大疾病，尤其癌症，密切相关。本项目拟设计组装新型多功能贵金属 纳米探针,赋予纳米探针高效检测miRNA的能力，结合纳米探针优良的光学和电化学性能，利用多种化学手段，原创性地提出一系列用于外周血和肿瘤细胞内miRNA 检测的新方法。探索可控有效地合成具有良好光、电性能的贵金属纳米材料；研究形状、大小与组成对其性能的影响；结合纳米材料的表面修饰技术，信号放大策略及生物分子识别技术，设计可用于miRNA 检测的多功能纳米探针，实现对外周血中miRNA的高效检测及肿瘤细胞中miRNA 的动态监测；同时探索药物、小分子干扰RNA等因素对miRNA 表达的影响。本项目将为miRNA生物分析及生物功能研究提供新方法与新技术，对于新的肿瘤标记物筛选和新药开发具有重要意义。

本项目合成多种具有良好光、电性能的贵纳米材料；设计多种 microRNA （miRNA）检测的多功能纳米探针；发展一系列基于多功能纳米探针miRNA检测方法；原创性地提出一系列用于外周血和肿瘤细胞内 miRNA 检测的新方法，构建了多种胞内miRNA检测方法及其生物功能的纳米药物。例如：发展DNA条形码与片段循环相结合的指数放大的miRNA灵敏检测技术；设计离子介导分子信标和目标片段循环放大侧裂，发展无标记的miRNA荧光传感器；基于高效的Pt/Sn-In2O3电化学探针，构建简便、快捷、灵敏的miRNA电化学检测的新方法；基于DNA四面体结构与特异性识别DNA-RNA链的DSN酶，发展miRNA灵敏多元的时检测的新方法。合成尺寸可控的二硫化钼量子，用于细胞多光子成像miRNA检测胞内检测；水热法可控合成石墨稀量子点，探索胞内miRNA检测及多基因乳腺癌细胞协同治疗；构建卟啉材料衍生物(P)/ PEG功能化的石墨烯量子点(GQD)对胞miRNA成像检测及光学治疗；发展多功能MoS2/Cu1.8S纳米诊疗平台用于多模式成像癌症诊断与光热/化学联合治疗。此外还构建了多种性能优良的电化学探针。本项目将为miRNA生物分析及生物功能研究提供新方法与新技术，对于新的肿瘤标记物筛选和新药开发具有重要意义。