基于上皮细胞内极化运输器设计纳米载体：出胞调控及其生物学效应

纳米技术为解决药物的口服吸收问题带来了极大的机遇，但其增加药物口服吸收的机制以及可能带来的生物安全性问题尚未阐明。在上一个基金纳米载体入胞及胞内转运路线调控研究基础上，本项目拟集中研究纳米载体跨极性上皮细胞的出胞调控以及出胞后可能产生的生物学效应。首先基于极性上皮细胞内极化运输路径构建多种极化运输分选信号肽修饰的纳米载体（靶向于普通循环内吞体，反式高尔基体管网状结构，基底膜），系统研究这些信号肽修饰的纳米载体在跨极性上皮细胞转运过程中的胞内运输与出胞行为，揭示有效促进纳米载体穿细胞转运的机制；然后研究纳米载体在跨过极性上皮细胞过程中对基底侧外泌体分泌的影响以及纳米载体可能的出胞状态，揭示纳米载体穿细胞后对下游组织造成影响的机制。该项目具有明显的创新性，对阐明纳米载体增加药物跨膜转运的机制以及生物安全性问题有重要意义。本团队在纳米技术增加药物跨膜转运方向有坚实的工作基础，完成任务的可行性强。

Nanotechnology brings great opportunities to solve the problems of drug absorption and the development of nanoproduct has achieved great progress. However, the mechanisms of nanocarriers improve drug absorption and the bio-safety after the transportation in polarized epithelial cells is limited understood. Based on the conclusion from endocytosis and intracellular transport pathway investigation supported by the previous fund, we will focuse on the transcytosis regulation and the subsequently biological effect in this project. First, we will design various nanocarriers modified by polarized traffic sorting signals, targeting to common recycling endosomes (CRE), trans-Golgi network (TGN) and basolateral membrane, to investigate how different signals influence the transport pathway and amount of nanocarriers. Furthermore, we will investigate how the transportation of nanocarriers influence the secretion of exosomes to elucidate the possible bio-safety problem resulted from the nanocarrier application. The project has obvious novelty, with great significance to clarify the mechanisms of how nanocarriers improve drug absorption and bio-safety. 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.