基于石墨烯选择性化学修饰的高效纳米药物载体的构筑及其在肿瘤光、热联合治疗中的性能研究

Due to the unique structural characteristics and large specific surface area, nano graphene has been considered as a promising drug carrier. However, the poor solubility of nano graphene limits its applications in biomedicine. To solve this problem, the graphenes have been strongly oxidized and chemically functionalized. Although increase the solubility, the oxygen-containing functional groups on the surface of graphene oxide (GO) significantly decrease the π-π interaction between GO and drug, reducing the drug loading capacity. In this project, a new nano drug carrier based on graphene (rather than GO) will be prepared through edge-functionalization. Since the flat structure of graphene is remained, and no oxygen-containing functional group is generated on the surface, we could expect a large amount of drug can be loaded through the π-π stacking interaction. The newly prepared nano drug carrier will be used in photo- and thermal- combined cancer therapy to obtain high cancer killing effect. This project will systematically investigate the effect of edge functional groups and polymer chain species on the solubility and drug loading capacity of the carrier. Meanwhile, we will try to understand how the carrier works in the whole cancer therapy process. The results of this research may develop a facile and novel method for fabricating nano drug carrier based on layered materials, and may promote the development of cancer therapy.

纳米石墨烯由于其独特的结构特性及大的比表面积，被认为是理想的药物载体之一。然而，差的溶解性极大限制了其在生物医药领域的应用。传统解决方法是将石墨烯氧化并进行化学修饰。氧化石墨烯表面的含氧基团，在增加溶解性的同时，也阻碍了其与药物分子之间的π-π堆积作用，使得载药量及治疗效率的提高受到限制。本项目通过对石墨烯边缘进行选择性化学修饰，构筑一种基于石墨烯（非氧化石墨烯）的纳米药物载体。由于石墨烯表面共轭结构保持完整，且无含氧基团阻挡，药物分子可以通过π-π堆积作用大量载入，从而获得高的载药量。新构筑的纳米药物载体将被用于肿瘤的光、热联合治疗，以期获得良好的治疗效果。本项目将系统讨论石墨烯边缘引入的活性官能团及接枝的高分子链的种类对载体溶解性及载药量的影响，探讨载体在光、热联合治疗中的作用机理，为层状纳米药物载体的构筑提供新思路与新方法，为推进肿瘤光、热治疗奠定基础。

碳纳米材料（如石墨烯、碳纳米管）由于具有独特的结构特性及大的比表面积，被认为是理想的药物载体。本项目以碳纳米材料及层状二硫化钼（MoS2）为纳米药物载体，通过π - π堆砌、疏水等非共价作用负载药物分子，从而获得高效的纳米载药体系，实现肿瘤的高效治疗。其中，开发的基于Ce6的纳米载药体系（G-Ce6和MoS2-Ce6），在用于肿瘤的光、热联合治疗时，杀死肿瘤细胞的能力比使用其他载药体系最高提高了10倍以上，对推进纳米材料在生物医药领域的应用研究具有重要的现实意义。