纳米金刚石仿生功能化及药物高效载带与缓控释性能研究

The development of simple, safe and efficient drug delivery systems is one of the frontier and hot research field in bionanotechnology. Based on our research background in biological effects of carbon nanomaterials and advantages in the field of biomaterials; we proposed surface modification of nanodiamond (ND) though mussel-inspired chemistry. Take advantage of the strong adhension of dopamine to materials and its chemical versatility，we for the first time investigate the surface modification of ND with dopamine. Then dopamine modified ND will be convalent linked with polyethylene glycol (PEG) and folic acid to investigate the effect of surface modification of ND on its pharmacokinetics and targeting performance. Finally, high effecienct loading cisplatin，controlled release of doxorubicin and cisplatin as well as their anti-tumor effeciency will also be investigated. This proposal is expected to solve problems in biomedical applications of ND，including difficult dispersion， low drug loading capacity as well as uncontrollable drug release. It will also provide novel idea for the development of new nano drug delivery systems.

发展简单、安全、高效的药物输运系统是当今纳米生物技术研究发展的前沿和热点。本项目以申请人前期在碳纳米材料生物效应研究领域中的工作为基础，结合课题组在生物材料领域的研究优势；提出了纳米金刚石仿生功能化的研究思路。利用多巴胺和材料的强粘附性和化学多功能性，研究多巴胺修饰的纳米金刚石聚乙二醇化和靶向分子连接；考察其药物长效靶向输运性能。以药物高效载带和缓控释应用为导向；利用纳米金刚石堆积形成的孔隙结构储存抗肿瘤药物阿霉素，再以聚多巴胺为包覆膜实现阿霉素缓释。另外，利用顺铂和羧基配位和pH值响应性，研究硫代苹果酸修饰的纳米金刚石-多巴胺复合材料对顺铂高效载带和pH值响应性释放。此课题不仅有望解决纳米金刚石生物医学应用中存在的分散困难、药物载带量低和难以实现药物控制性释放等问题，同时也为发展其它纳米药物输运系统提供新的研究思路。

纳米金刚石是一种生物相容性的碳纳米纳米材料，具有小尺寸、大比表面积以及特殊的荧光性能；在生物成像、活性物质细胞内输运、组织工程等方面具有潜在的应用。但是未经功能化的纳米金刚石在水溶液中容易团聚，因此进行表面功能化提高其水溶液分散性和赋予新的功能对于纳米金刚石的生物医学应用具有重要研究价值。 通过纳米金刚石表面偶联反应、表面引发原子自由基聚合以及表面活性剂包覆等手段，我们成功实现纳米金刚石的表面功能化。系统考察了这些功能化的纳米金刚石的水溶液分散性、生物相容性和药物输运性能。发表和纳米金刚石相关论文6篇；其它还有3篇以上论文待发表，待发表论文主要为纳米金刚石表面功能化影响对其代谢动力学的影响以及动物毒性评价等内容。