特异性适配体生物传感器靶向诊断肝癌的新技术研究

肝癌是临床上最常见恶性肿瘤之一，严重威胁人类健康和生命。寻找特异性与灵敏度更理想的肝癌诊断新技术是目前临床肝癌诊断研究领域的重点和难点。本项目拟以肝癌标志物AFP、GP73、DKK-1、Endoglin为靶点，利用本研究团队协同创新建立的高穿透力小分子引导肽CRISPR-Cas细胞基因编辑技术构建筛选适配体的细胞模型并筛选出相应的适配体。以适配体为识别探针，结合纳米材料的信号放大作用或示踪效应，构建石墨烯/血红素适配体纳米靶向探针，在血清学水平建立针对肝癌的多指标联合检测生物传感技术平台；构建荧光适配体纳米靶向探针，在病理组织学水平进行多指标组织标本荧光检测；构建磁性适配体纳米靶向探针，在影像学水平开展体内靶向肝癌磁共振成像诊断技术研究。本研究有望增强肝癌诊断方法的灵敏度和特异性，提高早期肝癌检出率，为肝癌的靶向诊断提供新思路，开辟新途径。

Hepatoma is one of the most common malignant tumors which severely threatens human health and life. Therefore, it is essential to discover some new ideal strategy of diagnosis and treatment with high sensitivity and specificity for hepatoma. In this project, the aptamers against hepatoma carcinoma markers AFP、GP73、DKK-1 and Endoglin were selected on the basis of the corresponding aptamers selection cell models prepared by CRISPR-Cas system with strong penetration of small molecule peptide guide, which was constructed by our research group. Then, the aptamers, which will be combined with nanomaterials thereby possessing the effect of signal-amplification or signal-tracing, will be used as probes to identify AFP、GP73、DKK-1 and Endoglin. Based on the technique, three sub-techniques will be developed. To be exactly, the graphene/hemin nano-probe will be developed to detect specifically AFP、GP73、DKK-1 and Endoglin in serum. Secondly, multi-target fluorescent detection will be used to detect in tissue specimen via the development of fluorescent aptamer nano-probe. Thirdly, the development of magnetic aptamer nano-probe will allow the research on diagnosis of hepatoma via in vivo hepatoma-targeted magnetic resonance imaging (MRI) to be achieved. Therefore, this study shows great possibility for improving sensitivity and specificity of diagnostic methods to increase detection rate of hepatoma. Furthermore, the research will provide new methods and ideas for targeting diagnosis of hepatoma.