基于微流控芯片的细胞间药物转运与化学信号传递研究

项目名称： 基于微流控芯片的细胞间药物转运与化学信号传递研究

项目编号： No.21275088

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 数理科学和化学

项目作者： 李海芳

作者单位： 清华大学

项目金额： 80万元

中文摘要： 细胞药物代谢研究是进行快速、低成本药物筛选的理想途径。常用的培养皿或微孔板式单一细胞药物代谢研究不能模拟生物体内多种组织和器官协同作用的药物代谢过程。本项目拟利用微流控芯片技术，进行细胞的共培养，模拟不同药物的肠细胞吸收、靶细胞作用和肝细胞代谢协同作用。分别以人体结肠癌Caco-2 细胞群来模拟小肠对药物吸收，以HepG2 肝癌细胞群模拟肝脏对药物的代谢，根据不同的药物选择相应的作用靶细胞，从而组建不同的代谢模拟体。利用荧光和高分辨质谱为检测手段，监测药物及其代谢物的吸收、转运和释放，考察药物受体蛋白和酶的促进或抑制作用，以及释放的细胞因子。从分子水平上研究细胞间的药物转运和化学信号传递，实现定性和半定量分析。

中文关键词： 微流控芯片；细胞共培养；药物代谢；药物转运；质谱检测

英文摘要： Cell-based drug metabolism is a perfect way for rapid and low-cost drug discovery. Conventional dish or bioassays just permits only one metabolic bioactivity depending on one singular cells, which can not simulate drug synergism like that of living tissues and organs. This project will employ microfluidic devices for cell co-culture and integrated simulation of intestinal absorption, target cell's bioactivity, and hepatic metabolism. For different drugs, different target cells and functional models are selected. The structural and mechanical models are composed of human colon cancer cells Caco-2 for intestinal absorption, human hepatocellular carcinoma cells HepG2 for hepatic metabolism, and target cells for bioactivity. Based on the fluorescent detection and high resolution mass spectrometry' identification, the processes of absorption, transport and release of drug and its metabolites will be monitored. Furthermore, the catalysis and inhibition of receptor protein and enzyme will be evaluated, and the released cytokines will be examined. The intercellular drug transfer and chemical signal transformation at molecular level will be qualitatively and semi-quantitatively monitored.

英文关键词： Microfluidic chip；cells cocultivation；drug metabolism；drug transport；MS analysis