Assessment of metabolism-dependent drug efficacy and toxicity on a multilayer organs-on-a-chip
文献类型：期刊论文
| 作者 | Li, Zhongyu1,2; Guo, Yaqiong1,2; Yu, Yue1,2; Xu, Cong1,2; Xu, Hui1,2; Qin, Jianhua1 |
| 刊名 | Integrative biology
 |
| 出版日期 | 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 |
| WOS记录号 | WOS:000386215400002 |
| 出版者 | ROYAL SOC CHEMISTRY |
| URI标识 | http://www.irgrid.ac.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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来源：中国科学院大学
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