可控纳米结构表面等离子体共振生物传感器的构建及肝癌早期检测研究

The proposed research intends to develop a new biosensor based on controlled gold nanorod composite for detection of Alpha-fetoprotein L3 (AFP-L3) of tumor marker and copper content in human serum with high sensitivity, diagnosing liver cancer early. The nano-composite may be more sensitive to the refractive index of the surrounding medium after the accomplishment of controlled preparation of gold nanorod composite and the adjustment of localized surface plasmon resonance, which will reveal the relationship between the surface plasmon resonance and gradually forming nanocomposite. Effects of complex biological components on gold nanorods functionalized with biological molecules will be studied in this project. The formed nanocomposites have unique optoelectronic properties and the ability to identify metal ion, showing the potential for the analysis of biological macromolecules and determination of the copper concentration. Therefore, a biosensor of joint detection of tumor marker and trace copper concentration can be fabricated. This biosensor will be further investigated with human serum samples to exhibit its advantages with fast, low-cost and high sensitivity. It is well known that the concentrations of AFP-L3 and copper existed in human serum vary with the developing process of liver cancer. This biosensor can detect biological macromolecule AFP-L3 in serum, but also the change of the copper concentration can be monitored in the process of liver cancer. The project will not only be able to overcome the limitation of single tumor marker in patients with lower positive rate, but also have some help on the assessment of pathological type. This study is expected to achieve the relative advantage of early detection of liver cancer.

本项目拟以血清中的肝癌标志物甲胎蛋白异质体（AFP-L3）和铜作为研究对象，构建连续检测复杂生物组分中AFP-L3和铜含量的高灵敏度生物传感，开展肝癌早期检测方法研究。通过金纳米棒复合物的可控制备和性质调控来提高对周围介质的敏感程度，考察复杂生物组分对功能化金纳米棒的表面等离子体性质调控影响，揭示纳米复合物的形成过程与表面等离子体性质调控之间的关系。基于这种多样结构特征纳米复合物独特的光电性质和对金属离子识别能力的特点，构建肝癌标志物和铜联合检测的生物传感器，以实际生物样品研究传感器的选择性、灵敏度等各项性能。血清中AFP-L3和铜的含量随着肝癌发展过程发生不同程度的变化，这种传感器既可检测血清中生物大分子AFP-L3浓度，又可监测肝癌发展过程中铜含量的变化。本项目的研究不仅可以克服单一肿瘤标志物诊断阳性率不高的局限性，而且对病理类型的评估也有一定的帮助，有望实现肝癌的相对早期检测优势。

恶性肿瘤发病率不断升高并已成为人类因疾病死亡的主要原因，癌症早期常无明显症状，难以明确诊断，提高癌症患者存活率的原则是早诊断、早发现、早治疗，其中最关键的是早期诊断。肿瘤标志物检测是目前肿瘤诊断最有效的方法之一，乳腺癌为世界范围内最常见的女性恶性肿瘤，男性前列腺癌发病率在我国急剧攀升。在本项目研究中，围绕可控纳米结构构建生物传感方法，我们进行了纳米结构复合物的可控制备及表面等离子体性质调控，合成了一系列可控纳米结构，以乳腺癌和前列腺癌的标志物作为研究对象，基于金纳米棒的局域表面等离子体共振性质，建立了高灵敏度检测乳腺癌和前列腺癌标志物等多组分的检测方法，通过金纳米棒负载不同抗肿瘤药物，分别用激光和化学方法诱导两种药物在乳腺癌细胞中的交替释放，并用荧光成像跟踪药物释放效果。合成了核壳纳米棒、金纳米簇、碳点以及含金碳点等可控纳米结构，系统研究了这些纳米簇的光谱性质，建立了纳米簇检测乳腺癌和前列腺癌患者血清中铜元素的荧光检测方法。进一步的研究表明这些纳米簇具有过氧化物酶的性质，纳米簇过氧化物模拟酶与天然酶相比，具有制备过程简单、容易大规模制备、性质稳定、可重复使用、对外界环境耐受性强、制造及储存成本低等优点。我们基于这些纳米过氧化物模拟酶发展了高灵敏度可视化检测血糖、乳腺癌标志物、前列腺癌标志物和毒品冰毒的可视化检测方法，取得了一批研究成果，在Analytical Chemistry等国际刊物发表SCI论文18篇，授权发明专利2项。本项目的研究不仅为多组分快速检测提供了一种思路，而且对病理类型的评估也有一定的帮助，有望实现恶性肿瘤的相对早期检测。