基于磁性碳纳米管的多功能纳米生物探针及其在肿瘤早期检测中的应用

It is significant to develop novel nano-bioprobe with high sensitivity and specificity for early detection and therapy of cancer. We first prepare superparamagnetic and targeted multifunctional antibody-conjuagetd magnetic carbon nanotube hybrids. By combining the advantages of the carbon nanotubes(CNTs) including high specific surface area and fast electron transfer ability together with good magnetic enrichment of magnetic nanoparticles as well as specific targeting of antibody biomolecues, a new type of highly sensitive and targeted electrochemical nanostructured immunosensor based on the CNT/ iron oxide hybrids is constructed by magnetic assembly method. Electrochemical and electrochemiluminescence techniques are employed to detect tumor cells and tumor markers quickly and sensitively. By taking advantage of high loading of superparamagnetic iron oxide nanoparticles with high magnetic susceptibility and targeting biomolecules on the surface of the CNT/ iron oxide bioconjugates, tumor cell-targeted magnetic resonance imaging（MRI） molecular probe based on multifunctional magnetic carbon nanotube bioconjugates is developed, and then used to specifically detect the trace amount of cancer cells by targeted cellular MRI enhancement effect. The strategies combining both electrochemistry and magnetic resonance imaging could offer great promise for sensitive, noninvasive, specific and early detection of cancer. Therefore, this research work will provide new strategies and valuable experimental foundamentals for developing these mulfunctional magentic carbon nanotube-based novel tumor-targeted molecular probe applied in the field of early dignosis of cancer.

发展高灵敏和特异性强的新型纳米生物探针技术对于癌症的早期检测和治疗有着重要的意义。首先合成具有超顺磁性和生物靶向的多功能磁性碳纳米管生物复合体。利用该复合体兼具碳纳米管大的比表面积和良好的电子传递性能、磁性纳米粒子良好的磁富集以及抗体生物分子的靶向性，通过磁性诱导组装法构建高灵敏、靶向特异识别的纳米电化学免疫生物探针，采用电化学和电化学发光技术进行肿瘤细胞和肿瘤标志物的快速灵敏检测研究。基于该复合体表面具有高负载量的超顺磁性与高磁化率的氧化铁纳米粒子和靶向生物分子的特点，开发靶向肿瘤细胞的多功能磁性碳纳米管磁共振分子影像探针，通过该分子探针特异性的磁共振成像（MRI）增强效应，以检测微量的早期癌细胞。本项目从电化学和影像学两个方面为癌症的早期、无创、灵敏、特异检测探索新途径，为研制开发基于多功能磁性碳纳米管的新型肿瘤分子探针在癌症早期诊断中的应用提供有重要参考价值的实验基础和理论依据。

本课题主要开展了电化学传感、电化学发光传感器、纳米分子影像探针和生物荧光探针的构建及其生物医学检测中的应用基础研究。成功构建了基于磁性碳纳米管、磁性石墨烯纳米粒子、三维结构的碳纳米管阵列、有序介孔碳、碳纳米球、片层状二硫化钼等功能纳米复合材料的电化学生物传感和电化学发光传感器，利用电化学技术、电化学发光技术、免疫技术以及磁调控组装技术，有效实现了对多种肿瘤标志物（如糖抗原CA19-9、癌胚抗原CEA、甲胎蛋白AFP等）、肿瘤细胞和药物分子等生物物质的高灵敏检测；设计合成了基于牛血清白蛋白（BSA）仿生合成的Pt@BSA、Au@BSA等纳米分子影像探针，生物有机荧光探针以及多功能纳米复合探针，为生物医学检测探索了良好的潜在应用平台。项目研究成果为开发高灵敏特异性的纳米检测新技术实现癌症等恶性疾病的早期快速检测提供了新策略和实验依据。