Investigation of Drug Cocktail Effects on Cancer Cell-Spheroids Using a Microfluidic Drug-Screening Assay
by
Ka I. Au Ieong 1,†, Chengpeng Yang 1,†, Chin To Wong 1, Angelie C. Shui 1, Tom T. Y. Wu 1, Ting-Hsuan Chen 1,2 and Raymond H. W. Lam 1,2,3,*
Ka I. Au Ieong 1,†, Chengpeng Yang 1,†, Chin To Wong 1, Angelie C. Shui 1, Tom T. Y. Wu 1, Ting-Hsuan Chen 1,2 and Raymond H. W. Lam 1,2,3,*
1
Department of Mechanical and Biomedical Engineering, City University of Hong Kong, Hong Kong, China
2
City University of Hong Kong Shenzhen Research Institute, Shenzhen 518057, China
3
Centre for Biosystems, Neuroscience, and Nanotechnology, City University of Hong Kong, Hong Kong, China
*
Author to whom correspondence should be addressed.
†
The authors contributed equally to this work.
Academic Editors: Xunli Zhang and Dario Carugo
Micromachines 2017, 8(6), 167; https://doi.org/10.3390/mi8060167
Received: 18 April 2017 / Revised: 18 May 2017 / Accepted: 19 May 2017 / Published: 24 May 2017
(This article belongs to the Special Issue Microfluidic Technologies for Drug Delivery)
Development of drugs based on potential anti-cancer chemotherapeutic agents has been hindered by its necessary tedious procedures and failure in the clinical trials because of unbearable toxicity and extremely low clinical efficacy. One of the technical challenges is the mismatch between laboratory settings and human body environments for the cancer cells responding upon treatments of the anti-cancer agents. This major limitation urges for applying more reliable platforms for evaluating drugs with a higher throughput and cell aggregates in a more natural configuration. Here, we adopt a microfluidic device integrated with a differential micromixer and multiple microwell-containing channels (50 microwells per channel) for parallel screening of suspending cell spheroids treated by drugs with different combinations. We optimize the culture conditions of the surfactant-coated microwells in order to facilitate the spheroid formation of the breast cancer cell line (MDA-MB-231). We propose a new drug cocktail combined with three known chemotherapeutic agents (paclitaxel, epirubicin, and aspirin) for the drug screening of the cancer cell-spheroids. Our results exhibit the differential responses between planar cell layers in traditional culture wells and cell-spheroids grown in our microfluidic device, in terms of the apoptotic rates under treatments of the drug cocktails with different concentrations. These results reveal a distinct drug resistance between planar cell layers and cell-spheroids. Together, this work offers important guidelines on applying the cell-spheroid microfluidic cultures for development of more efficacious anticancer drugs.
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Keywords:
microfluidic; toxicity; cell; cancer; drug screening
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MDPI and ACS Style
Au Ieong, K.I.; Yang, C.; Wong, C.T.; Shui, A.C.; Wu, T.T.Y.; Chen, T.-H.; Lam, R.H.W. Investigation of Drug Cocktail Effects on Cancer Cell-Spheroids Using a Microfluidic Drug-Screening Assay. Micromachines 2017, 8, 167.
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