基于芯片-质谱联用的肿瘤细胞药物代谢分析
详细信息 查看官网全文
- 英文论文题名：Study of Drug Metabolism of Tumor Cells Based on Microchip-MS
- 论文作者：李海芳 ; 介明沙 ; 林金明
- 英文论文作者：Hai-Fang Li ; Jieming Sha ; Jin-Ming Lin ; Department of Chemistry ; Tsinghua University
- 年：2016
- 作者机构：清华大学化学系;
- 论文关键词：芯片 ; 药物代谢 ; 质谱检测 ; 纳米金
- 英文论文关键词：Microchip ; Drug metabolism ; MS detection ; Au nanoparticles
- 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：R73-3
- 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：267k
- 原文格式：D
- 会议级别：全国
摘要
芯片与质谱联用是细胞分析的一种很好手段,高分辨质谱可以从复杂的化学背景干扰中筛选识别出微量的目标物。我们通过多层微流控芯片的设计,建立三种细胞的共培养体系,模拟伊立替康前体药物的肠细胞吸收、肝细胞代谢和脑胶质瘤细胞致凋亡作用。通过质谱分析发现HepG2肝癌细胞可以将伊立替康前体转化为活性中间产物7-乙基-10-羟基喜树碱(SN-38),显著增强药物对脑胶质瘤细胞U251细胞的致凋亡率。与细胞耐药性密切相关,可指示细胞受损和凋亡状态的生物标志物谷胱甘肽(Glutathione,GSH)在样品处理过程中很容易被氧化成氧化态的GSSG型(glutathione disulfide)。研究发现,Au-Ag NPs/Nano Si表面可特异性地富集GSH,且具有很好的激光解吸电离辅助效应,应用于细胞中GSH的SALDI-MS分析,有效避免了GSH的氧化反应干扰。
The combination of microchip with mass spectrometry becomes an ideal tool for cell analysis.The high resolution mass spectrometer could selectively screen and identify trace chemical targets from complex background.The multi-layer microfluidic device was designed to co-culture three different types cells to mimic irinotecan intestine cells absorption,liver cell metabolism,and targeting glioblastoma cells.It was revealed that the prodrug irinotecan was transformed to more active SN-38 by HepG2 cells to induce the death of glioblastoma cells.Glutathione(GSH),a biomarker to indicate the state of the cell damage and apoptosis,played an important role for drug resistance of cells.The oxidization of GSH to GSSG during sample pretreatment made it difficult to get accurate measurement.In the research,the modified Au-Ag NPs/Nano Si chip could selectively and rapidly collect GSH from cell lysate and presented matrix function for SALDI-MS detection.
The combination of microchip with mass spectrometry becomes an ideal tool for cell analysis.The high resolution mass spectrometer could selectively screen and identify trace chemical targets from complex background.The multi-layer microfluidic device was designed to co-culture three different types cells to mimic irinotecan intestine cells absorption,liver cell metabolism,and targeting glioblastoma cells.It was revealed that the prodrug irinotecan was transformed to more active SN-38 by HepG2 cells to induce the death of glioblastoma cells.Glutathione(GSH),a biomarker to indicate the state of the cell damage and apoptosis,played an important role for drug resistance of cells.The oxidization of GSH to GSSG during sample pretreatment made it difficult to get accurate measurement.In the research,the modified Au-Ag NPs/Nano Si chip could selectively and rapidly collect GSH from cell lysate and presented matrix function for SALDI-MS detection.
引文
1.D.Gao,H.Liu,Y.Jiang,J.-M.Lin,Trends Anal.Chem.,2012,35:150-164.
2 .A.M.Skelley,O.Kirak,H.Suh,R.Jaenisch,J.Voldman,Nat.Methods,2009,6:147-152.
3 .D.Gao,H.-F.Li,N.Wang,J.-M.Lin,Anal.Chem.,2012,84:9230-9237.
4 .S.Mao,J.Zhang,H.-F.Li,J.-M.Lin,Anal.Chem.,2013,85:868-876.
5 .L.Richard,B.M.Philip,Anal.Chem.2009,81:7047–7056.
2 .A.M.Skelley,O.Kirak,H.Suh,R.Jaenisch,J.Voldman,Nat.Methods,2009,6:147-152.
3 .D.Gao,H.-F.Li,N.Wang,J.-M.Lin,Anal.Chem.,2012,84:9230-9237.
4 .S.Mao,J.Zhang,H.-F.Li,J.-M.Lin,Anal.Chem.,2013,85:868-876.
5 .L.Richard,B.M.Philip,Anal.Chem.2009,81:7047–7056.