基于硼酸酯键和纳米金信号放大技术构建癌症标志物电化学传感器

Early diagnosis and treatment of cancer is one of the hot topics of current research. MicroRNAs and glycoproteins are believed to be important for cancer diagnosis and prognosis serving as reliable molecular biomarkers. Therefore, simple, sensitive, and cost-effective assays for microRNAs and glycoproteins are in urgent demand. The main difference in the structure of RNA versus DNA is the presence of a hydroxyl group at the 2' position of the ribose sugar in RNA, which makes the RNA molecule contain cis-diol at the end of the chain. Also, glycoproteins contain diol groups in the oligosaccharide chains covalently attached to polypeptide side-chains. Hydrophilic boronic acids are well known to form tight boronate ester covalent bonds with diols. In view of these properties and the merits of electrochemical biosensors, we attempted to develop electrochemical biosensors for the detection of microRNAs and glycoproteins. Specifically, miRNAs and glycoproteins are captured by the pre-immobilized DNA probes at the gole electrode, respectively, and then derivatized with boronic acid-containing compounds through the formation of boronate ester bonds for the attachment of electrochemically active tags. Gold nanoparticles will be employed in this project to enhance the sensitivity. We believe that our work will be valuable for the design of electrochemical biosensors and the early diagnosis and progression of cancer.

癌症的早期诊断和治疗是当前研究的热点课题之一，癌症标志物的检测是癌症早期诊断的重要依据。MicroRNAs和糖蛋白是某些癌症的生物标志物。基于电化学传感器的优势以及申请小组在表面分析与生物传感方面的研究经验，本项目拟根据microRNAs和糖蛋白的结构特点构建几种电化学传感器。MicroRNAs的3'端的糖基含有顺式邻二醇基团，糖蛋白含有一个或多个糖基，根据邻二醇和硼酸之间硼酸酯键的形成和纳米金信号放大的性质，本项目拟采用探针DNA修饰的电极捕获microRNAs或糖蛋白，再利用具有单（多）硼酸基团的物质识别microRNAs或糖蛋白，最后利用电活性物质修饰的纳米金进行信号放大输出，构建快速灵敏、免标记检测microRNAs和糖蛋白的电化学传感器，为癌症的早期诊断提供一种有效的手段。本项目对癌症的预防和治疗具有十分重要的意义。

癌症标志物的检测是癌症早期诊断的重要依据。MicroRNAs和糖蛋白是某些癌症的生物标志物。本项目的主要研究内容是根据microRNAs和糖蛋白的结构特点及纳米金信号放大技术构建几种电化学传感器。该研究内容已经按计划执行并完成。MicroRNAs的3'端的糖基含有顺式邻二醇基团，糖蛋白含有一个或多个糖基，根据邻二醇和苯硼酸之间硼酸酯键作用和纳米金/银信号放大的性质，本项目采用探针DNA修饰的电极捕获microRNAs或糖蛋白，再利用苯硼酸衍生物或苯硼酸修饰的纳米粒子对microRNAs或糖蛋白进行衍生，最后利用酶催化或电活性纳米粒子进行信号放大输出，构建快速灵敏、免标记检测microRNAs和糖蛋白的电化学传感器，为癌症的早期诊断提供了一种有效的手段。此外，本项目研究还建立了蛋白酶活性分析及其抑制剂筛选的新技术；提出了“电化学-化学”和“电化学-化学-化学”氧化还原循环体系；基于金银纳米粒子比色分析的原理，建立了新型的电化学传感器，实现了多种疾病标志物的灵敏检测。