集成微流控细胞共培养系统和模拟药物的代谢
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- 英文论文题名：Integrated microfluidic system for cell co-culture and simulation of drug metabolism
- 论文作者：介明沙 ; 李海芳 ; 林路遥 ; 张洁 ; 林金明
- 英文论文作者：Mingsha Jie ; Hai-Fang Li ; Luyao Lin ; Jie Zhang ; Jin-Ming Lin ; State Key Laboratory of Chemical Resource Engineering ; Beijing University of Chemical Technology ; Department of Chemistry ; Beijing Key Laboratory of Microanalytical Methods and Instrumentation ; The Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology ; Tsinghua University
- 年：2016
- 作者机构：北京化工大学化工资源有效利用国家重点实验室;清华大学化学系微量分析测试方法与仪器研制北京市重点实验室;
- 论文关键词：微流控芯片 ; 细胞共培养 ; 伊立替康代谢 ; LC-MS/MS检测
- 会议召开时间：2016-07-01
- 会议录名称：中国化学会第30届学术年会摘要集-第四十三分会：质谱分析
- 语种：中文
- 分类号：TQ460.1
- 学会代码：ZGHY
- 会议名称：中国化学会第30届学术年会-第四十三分会 ; 质谱分析
- 会议地点：中国辽宁大连
- 主办单位：中国化学会
- 学会名称：中国化学会
- 页数：1
- 文件大小：142k
- 原文格式：D
- 会议级别：全国
摘要
本研究以微流控芯片为平台,进行前体药物伊立替康(CPT-11)的肠细胞吸收、靶细胞作用和肝细胞代谢协同药物代谢研究:分别以人结肠癌Caco-2细胞群体来模拟小肠对药物吸收,以HepG2肝癌细胞群体模拟肝脏对药物的代谢[1]。CPT-11需要经过Caco2细胞吸收,HepG2细胞代谢形成活性中间产物7-乙基-10-羟基喜树碱(SN-38),活性药物再进入靶器官U251细胞代谢产生抗癌效果。利用荧光检测、流式细胞仪和液相色谱与串联质谱等技术检测药物代谢过程中的代谢产物[2],构建功能化的药物代谢微流控芯片系统,实现细胞间药物转运与化学信号传递的监控。这一3D装置可推广用于体外药物筛选及个性化癌症治疗的研究。
In this work,a multi-type cell microfluidic integrator for cocultivation enabling simulation of drug absorption,metabolism,and anticancer activity was developed.To organize an in vitro drug absorption and metabolism model,Caco-2,HepG2,and U251 cells were co-cultured as mimic organs of the intestine,liver,and glioblastoma,respectively.The drug cytotoxicity assay was monitored by fluorescence visualization.The extra-/intra-cellular CPT-11 and its active metabolite of 7-ethyl-10-hydroxycamptothecin(SN-38) were qualitatively and quantitatively characterized by liquid chromatography-tandem mass spectrometry.Our results suggested that this dynamic 3D device provided a potential application for high throughput drug screening and personalized cancer therapy.
In this work,a multi-type cell microfluidic integrator for cocultivation enabling simulation of drug absorption,metabolism,and anticancer activity was developed.To organize an in vitro drug absorption and metabolism model,Caco-2,HepG2,and U251 cells were co-cultured as mimic organs of the intestine,liver,and glioblastoma,respectively.The drug cytotoxicity assay was monitored by fluorescence visualization.The extra-/intra-cellular CPT-11 and its active metabolite of 7-ethyl-10-hydroxycamptothecin(SN-38) were qualitatively and quantitatively characterized by liquid chromatography-tandem mass spectrometry.Our results suggested that this dynamic 3D device provided a potential application for high throughput drug screening and personalized cancer therapy.
引文
[1]Esch,E.W.;Bahinski,A.;Huh,D.Nat Rev Drug Discov.2015,14:248.
[2]Mao,S.;Zhang,J.;Li,H.;Lin,J.-M..Anal.Chem..2013,85:868.
[2]Mao,S.;Zhang,J.;Li,H.;Lin,J.-M..Anal.Chem..2013,85:868.