受体介导的纳米载体在极性上皮细胞的跨膜转运机理研究

纳米技术为解决药物吸收问题带来了极大的机遇，其产品开发也取得了很大进展，但纳米载体增加药物口服吸收的机理包括影响纳米载体跨膜转运的因素等尚未阐明。面对纳米载体跨膜转运的众多科学问题，本项目拟集中研究配体修饰对纳米载体跨极性上皮细胞转运的影响。本项目拟选择三种类型的配体(FcBP:靶向于FcRn,与受体结合后具有单向跨膜转运功能;7pep:靶向于TfR,该受体在胞内转运具有循环功能;环状RGD:靶向于Integrin，与受体相互作用主要是增加载体与细胞的黏附)修饰高分子胶束，采用激光共聚焦显微镜，荧光共振能量转移、表面等离子体共振、等温滴定量热法等新技术，研究不同类型的受体以及配体与受体的亲和性对胶束跨膜转运途径、速度以及量的影响。该项目有明显的创新性，对阐明纳米载体增加药物跨膜转运的机理有重要意义。本团队在纳米技术增加药物跨膜转运领域有丰富的经验和坚实的基础，科研力量强，完成的可行性较强。

Nanotechnology brings great opportunities to solve the problems of drug absoroption and the development of nanoproduct has achieved great progress. However, the mechanisms of nanocarriers improve drug absorption including the factors influencing the transport of nanocarriers in polarized epithelial cells is limit understood. Among so many scientific problems in transmembrane transportation, we will focuse on studying the transport mechanisms of receptor medicated nanocarriers in polarized epithelial cells. Three types of ligands (targeting to there types of receptors) will be selected (FcBP：targeting to FcRn，with single direction transport character after binding with receptor；7pep：targeting to TfR，with recycling transport pathway in cells；Cyclic RGD：targeting to Integrin，mainly improve the affinity of carriers with cells) to modify polymeric micelles. We will apply some novel technology such as confocal, FRET, SPR, ITC, to investigate how different receptor types, affinity between ligands and receptors influence the transport pathway, transport rate and amount of nanocarriers. The project has obvious novelty, with great significance to clarify the mechanisms of how nanocarriers improve drug absorption. We have rich experience and solid foundation in the study on how nanotechnology improves drug transmembrane transportation. We have a rational research team and have great possibility to accomplish the project.