基于肿瘤多模诊治的黄金碳纳米管的制备及性能研究

Some nanomaterials with special optical, thermal and maganetic properties can significantly improve the sensitivity and specificity of existing diagnostic and therapeutic technique. They have become an important part of tools for cancer diagnosis and therapy. In this project, we propose to prepare a particular core-shell golden carbon nanotube by coating gold nanoparticles onto the surface of multilayer polysaccharides functionalized carbon nanotubes. The quantum coupling and synergistic effect of carbon nanotubes and gold nanoparticles improve the Raman signals and photothermal conversion of carbon nanotubes, and increase the efficiency of gold nanoparticles for the contrast-enhanced X-ray computed tomography (CT) imaging. The resulting golden carbon nanotubes show enhanced properties in both Raman/CT imaging and photothermal therapy. In addition, the photothermal effect can accelerate the release of attached anticancer drugs from the surface of carbon nanotubes and improve the effect of chemotherapy. With further surface modification by targeting molecules, the golden carbon nanotubes therefore can remarkably increase the sensitivity for cancer diagnosis and the efficiency of therapy. It provides a new concept of multimodal platform for the enhanced Raman/CT imaging with the overlap of enhanced photothermal therapy, which giving clinics with more flexibility. We will also investigate following fundamental issues: 1) Systematically study of the multilayered self-assembly of polysaccharides on carbon nanotubes and the controlled growth of noble metal nanoparticles on the surface of polysaccharides functionalized carbon nanotubes; 2) The impact of nano-assembly and hybridization to the photothermal property and Raman/CT imaging; 3) Establishing appropriate technology to evaluate and investigate the biomedical properties of golden carbon nanotubes including toxicity, targeting capacity, Raman/CT contrast and photothermal/reinforcing thermotropic chemotherapy properties both in vitro and in vivo.

一些具有光、热、磁特性的纳米材料可增强现有诊断和治疗技术的灵敏性和特异性，已成为癌症诊断和治疗的有力手段。本项目提出在多糖改性的碳纳米管表面生长一层金纳米粒子获得一类黄金碳管。由于金纳米粒子和碳管的协同作用，能增强碳管的Raman信号和光热转化能力，并增强金纳米粒子CT造影能力，使得黄金碳管兼有增强的Raman/CT多模诊断和光热疗特性。另外光热效应还能促进碳管表面药物的快速释放，增强化疗效果。因此黄金碳管能显著提高肿瘤诊断的灵敏度并实现同步的多模累加治疗，为临床提供更好的选择。本项目还将系统研究多糖对碳管多层组装改性及其它贵金属纳米粒子在多糖表面可控生长的技术和机理；纳米组装与杂化对光热转化和Raman/CT特性的影响规律；最后建立合适的评价技术与方法分别在细胞和动物水平研究黄金碳管的毒性、靶向性能、增强Raman/CT造影诊断和光热疗/热致增强化疗等性能。

本项目按照预定的研究内容和研究目标，很好或超额完成了研究任务：除了设计制备了一系列具有光热疗/热致增强化疗多重治疗能力的贵金属功能化碳纳米管，在细胞和裸鼠水平实现肿瘤的多模靶向治疗。还完成了一系列其他光热功能高分子对碳管的包覆改性，还制备了一系列具有光热特性或荧光/CT/MRI特性的无机纳米粒子，载药和表面修饰后同样实现了肿瘤的多模诊断和同步治疗。系统的研究金纳米粒子功能化碳管等纳米药物在制备及其在生物应用中的一些基本科学问题，如贵金属纳米粒子在碳管表面可控生长制备技术；表面生物相容性和靶向性能修饰改性技术；研究了贵金属纳米粒子的间距、表面性能、与碳管的相互作用等对SPR吸收等性能的影响规律。实现了多功能纳米粒子在肿瘤诊疗中应用潜能的评价。研究成果主要以论文和专利形式体现，共发表影响因子大于4.0的相关论文15篇（原定目标6-10篇），并获批国家发明专利1项（原定目标申请1-2项）。培养博士生2人（计划培养博士和硕士生2－5人）。