期刊
BIOSENSORS & BIOELECTRONICS
卷 68, 期 -, 页码 322-328出版社
ELSEVIER ADVANCED TECHNOLOGY
DOI: 10.1016/j.bios.2015.01.013
关键词
Microchip; Cell co-culture; Hepatic metabolism; Capecitabine; MS detection
类别
资金
- National Natural Science Foundation of China [81373373, 21275088, 91213305]
- China Equipment and Education Resources System [CERS-1-75]
In this work, an in vitro liver model in a microfluidic device to imitate and detect prodrug metabolism was developed. A widely used prodrug capecitabine (CAP), which needs to be metabolized into active intermediate in the liver and then transformed into final effective drug in tumor cells, was selected as a model compound. The microfluidic device we exploited consists of a cell co-culture section, in which HepG2 cells were cultured to represent liver while MCF-7 cells were used to represent the tumor tissue, and an on-line solid phase extraction (SPE) section connecting to the ionization source of the ESI-Q-TOF mass spectrometer. The prodrug metabolism was realized and confirmed within this in vitro liver model as the intermediate product of the prodrug 5 '-deoxy-5-fluorouridine (DFUR) was successfully detected with MS after the conditioning of HepG2 cells, and the anti-tumor effect of the active metabolite was observed through cell vitality assays of MCF-7 cells. The limit of detection (LOD) using on-chip SPE was at 10 nM and semi-quantitative analysis could be realized. This system has been proved useful and practical, showing a potential to replace conventional drug screening methods. (C) 2015 Elsevier B.V. All rights reserved.
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