多色纳米探针对卵巢癌肿瘤miRNA的多组分测定与成像

Early diagnosis and treatment of ovarian cancer are the keys to improve patient survival rate.But the majority of ovarian cancer patients are diagnosed with advanced disease, at which time prognosis and survival rates are worse. Therefore it is important to develop new screening strategies for the early detection of stage I ovarian cancer. Tumor-related miRNAs are emerging as a novel class of cancer biomarkers. The levels of tumor miRNAs in serum and cell are associated with the stages of tumors, and reliable and sensitive determination of tumor-related miRNAs plays a significant role in early cancer screening and evaluation. Here we propose a novel strategy for simultaneous detection of multiple miRNAs targets, which would bring new opportunities for improving the accuracy of early ovarian cancer detection. Based on the emerging nanotechnology and biotechnology, we developed a novel nanocomposite multicolor fluorescence probe with combines the unique fluorescence properties of quantum dots and good specificity of synthetic oligonucleotides. The proposed nanoprobe can simultaneously detect and image multiple types of tumor-related miRNAs in serum and living cells with excellent sensitivity and specificity. The interaction mechanism between nanoprobe and analytes is detailedly studied. We anticipate that the project research could offer more comprehensive and reliable information for screening early-stage ovarian cancer.

卵巢癌的早期诊断与治疗，对提高患者的治愈率具有十分重要的意义。但目前我国的卵巢癌确诊病人多数已是中晚期，错过了最佳治疗时期，因此寻找新的诊断方案是目前亟待解决的问题。miRNA是一类新发现的肿瘤标志物，其在血清或细胞内表达水平的变化与肿瘤的发生、发展进程密切相关，多种特异miRNA的联合检测对卵巢癌的早期诊断及疗效预测等方面具有较大的实用价值。本项目基于新兴的纳米技术和生物技术，着眼于卵巢癌肿瘤miRNA多组分检测技术的开发，通过纳米结构设计以及与待测标志物有特异识别的基因分子结构设计，发展对卵巢瘤miRNA具有超灵敏度和高特异识别能力的多色纳米复合探针，实现血清中及细胞内多种miRNA肿瘤标志物的同时检测和成像，研究纳米探针与待测分子之间的作用机制，为卵巢癌早期诊断、预后判断等新方法的研究提供理论指导和技术支持。

氨基酸、蛋白质等生物分子及离子（Fe3+等）对维持生命的正常运行具有重要作用。它们在体内含量的变化预示着健康水平的变化，其过量或缺失都将会导致生理的异常和疾病的产生。发展高效的分子探针，对生物样品中的特定分子或离子的实时含量进行准确、快速、高选择性地检测，对于医学、分子生物学都有着非常重要的意义。本研究基于新兴的纳米技术和生物技术，合成了一系列光稳定性好、粒径分布窄、生物相容性好、高质量的荧光量子点及银纳米颗粒；以所制备的荧光量子点和银纳米粒子为研究平台，通过对纳米粒子表面结构的调控，构建高性能的比色纳米探针、荧光纳米探针和荧光-磁共振双模态纳米探针，建立对细胞及生理环境中半胱氨酸、铁蛋白、Fe3+和卵巢癌HE4肿瘤标志物的超敏感定量检测与成像方法；具体量化各个影响因素对检测的影响，研究定量关系及探针与靶分子的作用机制。研究结果显示所构建的纳米探针具有稳定性好、检测灵敏度高、使用方便等优点，在对疾病的早期检测、指导治疗干预、患者的生存预后、以及抗肿瘤治疗反应的预测等领域具有较大的应用前景。