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	Assessment of metabolism-dependent drug efficacy and toxicity on a multilayer organs-on-a-chip
	Li, Zhongyu1,2; Guo, Yaqiong1,2; Yu, Yue1,2; Xu, Cong1,2; Xu, Hui1,2; Qin, Jianhua1
刊名	Integrative biology
	2016
卷号	8期号:10页码:1022-1029
ISSN号	1757-9694
DOI	10.1039/c6ib00162a
通讯作者	Qin, jianhua(jhqin@dicp.a.cn)
英文摘要	Pharmaceutical development is greatly hindered by the poor predictive power of existing in vitro models for drug efficacy and toxicity testing. in this work, we present a new and multilayer organs-on-a-chip device that allows for the assessment of drug metabolism, and its resultant drug efficacy and cytotoxicity in different organ-specific cells simultaneously. four cell lines representing the liver, tumor (breast cancer and lung cancer), and normal tissue (gastric cells) were cultured in the compartmentalized micro-chambers of the multilayer microdevice. we adopted the prodrug capecitabine (cap) as a model drug. the intermediate metabolites 50-deoxy-5-fluorocytidine (dfur) of cap that were metabolized from liver and its active metabolite 5-fluorouracil (5-fu) from the targeted cancer cells and normal tissue cells were identified using mass spectrometry. cap exhibited strong cytoxicity on breast cancer and lung cancer cells, but not in normal gastric cells. moreover, the drug-induced cytotoxicity on cells varied in various target tissues, suggesting the metabolism-dependent drug efficacy in different tissues as exisits in vivo. this in vitro model can not only allow for characterizing the dynamic metabolism of anti-cancer drugs in different tissues simultaneously, but also facilitate the assessment of drug bioactivity on various target tissues in a simple way, indicating the utility of this organs-on-chip for applications in pharmacodynamics/pharmacokinetics studies, drug efficacy and toxicity testing.
WOS关键词	THYMIDINE PHOSPHORYLASE ; MICROFLUIDIC DEVICE ; IN-VITRO ; CELL-CULTURE ; HUMAN LIVER ; C-ELEGANS ; CAPECITABINE ; CANCER ; MODELS ; 5-FLUOROURACIL
WOS研究方向	Cell Biology
WOS类目	Cell Biology
语种	英语
出版者	ROYAL SOC CHEMISTRY
WOS记录号	WOS:000386215400002
内容类型	期刊论文
URI标识	http://www.corc.org.cn/handle/1471x/2375012
专题	中国科学院大学
通讯作者	Qin, Jianhua
作者单位	1.Chinese Acad Sci, Dalian Inst Chem Phys, Div Biotechnol, Dalian, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
推荐引用方式 GB/T 7714	Li, Zhongyu,Guo, Yaqiong,Yu, Yue,et al. Assessment of metabolism-dependent drug efficacy and toxicity on a multilayer organs-on-a-chip[J]. Integrative biology,2016,8(10):1022-1029.
APA	Li, Zhongyu,Guo, Yaqiong,Yu, Yue,Xu, Cong,Xu, Hui,&Qin, Jianhua.(2016).Assessment of metabolism-dependent drug efficacy and toxicity on a multilayer organs-on-a-chip.Integrative biology,8(10),1022-1029.
MLA	Li, Zhongyu,et al."Assessment of metabolism-dependent drug efficacy and toxicity on a multilayer organs-on-a-chip".Integrative biology 8.10(2016):1022-1029.

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