基于超分子主体/鳞片状MnO2纳米复合材料的电化学生物传感器的构建及其在新型肿瘤标志物检测中的应用

Recent studies have demonstrated that a gene can produce message RNA (mRNA) isoforms with 3’ untranslated regions (3’UTRs) of different length. Genes undergoing 3’UTR shortening could become useful novel biomarkers and potentially targeted for disease prevention and treatment. In comparison to conventional detection methods, electrochemical determination has obvious advantages including high efficiency, good sensitivity, speediness, and low-cost. However, electrochemical determination of the novel tumor markers has never been reported. In the present study, 6 tumor molecular markers (short 3’UTR mRNA) of breast and lung cancers were selected as target genes and the electrochemical determination for short 3’UTR Dicer 1 mRNA, one of the target genes, was successfully performed in our previous study. To construct this biosensor, 1) supramolecular host compounds, such as calixarene 6 (CX6) or cucurbituril 7 (CB7) will be used as molecular device to improve molecular recognition ability; 2) Au@TiO2 composite at surface of graphene will be used to immobilize biomolecule; and 3) capture probe will be assembled to the surface of nanocomposite through signal amplification using nanocomposite of Pd@MnO2. The short 3′UTR mRNA contents in 10 breast cancer cell lines and 5 lung cancer cell lines will be determined by the constructed sensor. The reliability of the content of 3’UTR mRNA based on the constructed electrochemical biosensor will be evaluated using traditional real-time PCR method. The results may widen the usage of supramolecules, such as CX6 and CB7 in biosensors and will provide new thoughts and theoretical foundation for the development and utilization of biosensors. Furthermore, the results may also lay foundation for the detection of tumor biomarkers and diagnostic of cancer.

重要基因产生的带有短3′非编码区（3′UTR）的转录产物是新近报道的一类新型肿瘤标志物。与该肿瘤标志物的常规检测方法相比，电化学检测法突显出高效、灵敏、快速、廉价等优点，然而相关研究还未见报道。在前期对Dicer1基因3′UTR电化学研究的良好基础上，本项目拟用超分子主体化合物杯芳烃6或葫芦脲7作为分子器件，将Au@TiO2@石墨烯复合纳米载体标记固定生物分子，通过Pd@MnO2纳米复合材料放大检测信号，将捕获探针组装到复合膜的表面构建CP/Au/Pd@MnO2/GCE生物传感器，检测乳腺癌和肺癌细胞株中6个肿瘤标志物的含量，并用传统的生物学方法进行评估，最终确立新型肿瘤标志物的电化学检测方法。该研究可拓宽超分子主体杯芳烃及葫芦脲作为分子器件在生物传感器中的应用，将对生物传感器的发展提供新的思路和理论依据，同时为新型肿瘤标志物的检测及相关疾病的诊断奠定基础。

重要基因产生的带有短3′非编码区（3′UTR）的转录产物是新近报道的一类新型肿瘤标志物。与该肿瘤标志物的常规检测方法相比，电化学检测法突显出高效、灵敏、快速、廉价等优点，然而相关研究还未见报道。在前期对Dicer1基因3′UTR电化学研究的良好基础上，本项目拟用超分子主体化合物杯芳烃、柱芳烃以及葫芦脲作为分子器件，将Au@TiO2@石墨烯、磷烯等复合纳米载体标记固定生物分子，通过Pd@MnO2纳米复合材料放大检测信号，将捕获探针组装到复合膜的表面构建CP/Au/Pd@MnO2/GCE生物传感器，检测了乳腺癌和肺癌细胞株中肿瘤标志物的含量，并用传统的生物学方法进行评估，最终确立新型肿瘤标志物的电化学检测方法。该研究极大地拓宽了超分子主体杯芳烃及葫芦脲作为分子器件在生物传感器中的应用，将对生物传感器的发展提供新的思路和理论依据，为新型肿瘤标志物的检测及相关疾病的诊断奠定基础。另外，在完成拟定的研究任务的基础上，创新性地把本项目中制备的纳米复合材料及超分子识别原理应用于其他物质的荧光或电化学检测，开辟了其新的应用途径。. 项目研究成果在Biosens. Bioelectron., Chem. Commun.; Nanoscale; Sens. Actua. B: Chem.; Analyst等国际知名学术刊物上共发表论文17篇学术论文（其中SCI论文16篇，中文受邀综述1篇），论文总影响因子大于90，中科院JCR1区论文10篇，影响因子大于5的论文10篇，该一系列的研究工作得到了国际同行的高度认可。