中文摘要
纳米载药系统是当今临床治疗最具先进性的给药形式之一,通过改变药物的体内过程而表现出诸多优越性。但复杂的体内环境,使纳米载药系统需要跨越由不同细胞构成的多种生物屏障,才能将药物转运到靶部位;而纳米系统与细胞屏障发生相互作用后的稳定性,也使其细胞内过程分析成为药物分析领域的一个研究瓶颈,因此,清楚解析纳米系统的细胞转运机理对于阐释其体内行为具有重要意义。本研究基于“双细胞+双示踪”的设计理念,着眼于“纳米载药系统整体的多细胞转运行为”这一关键环节,构建双标记纳米载药系统和双细胞转运模型,建立一种非侵入式、实时、灵敏的细胞水平的荧光示踪分析方法。综合分析纳米载药系统与细胞质膜的相互作用、被细胞内吞/外排的途径、经共培养细胞模型转运的特点和动力学过程,以期阐明纳米系统在细胞内的行为和跨膜转运的机理,为纳米载药系统在细胞水平的过程研究提供新思路和新方法。
英文摘要
Nano drug delivery system has been one of the most advanced administrations for clinical therapy. Nano delivery system exhibits numerous advantages due to alter dynamics processes of drug in vivo. However there are a few questions in complex environment in vivo, for example, whether nano drug delivery system can pass through many barriers consisting of different epithelium cells and connective tissues before they are taken up by the target cells, and whether they are stable in the process of crossing these barriers. In addition, it that the research about the interaction between nano drug delivery system and cell becomes urgent need to solve a scientific problem for pharmaceutical analysis. So, the further study about the mechanisms of adsorption, uptake and trans-membrane of nano system in cell are very meaningful to interpret the behavior of nano drug delivery system in vivo. This study will be based on the design concept of “a co-culture cell model and a double fluorescence labeling technique” and focus on the key link of “the transport processes of the whole nano drug delivery system in a co-culture cell model”. The aim is to develop a non-invasive, real-time and sensitive analysis method using the fluorescence molecular imaging technology, and this method can be used for continuously and dynamically monitoring the behaviors of nano drug delivery system in living cell. In this study, the interaction between nano drug delivery system and cell surface will be analyzed, the pathway of endocytosis and efflux of nano system in cell and the characteristics of the trans-epithelial cell transport will be also investigated. Moreover, the dynamic processes of nano system in cell will be visualized. A new idea and way will be provided for study the behavior of nano drug delivery system in living cell.
