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Investigation into the hypoxia-dependent cytotoxicity of anticancer drugs under oxygen gradient in a microfluidic device

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Abstract

Oxygen tension is essential for cellular activities and plays an important role in clinical cancer treatment. In this paper, we constructed a single-layer microfluidic device with oxygen gradients to study oxygen-dependent cytotoxicity of anticancer drugs. Oxygen concentrations in the cell culture chamber are controlled by spatially confined oxygen-scavenging chemical reaction in the neighboring microfluidic channel. The groove-shaped structure of PDMS membrane is designed to increase its bonding ability to the bottom layer, which helps avoid the leakage of liquid while facilitating the exchange of gas between the cell culture chamber and the reaction channel. For demonstration, A549 cells were cultured in the microfluidic device and treated with tirapazamine (TPZ) or cisplatin under various oxygen contents. An increase in apoptosis of A549 cells was observed due to the hypoxia-induced cytotoxicity of TPZ, which provided evidence that anticancer efficiency of TPZ is influenced by oxygen tensions directly and have great promise in selectively killing tumor cells in hypoxic microenvironment. Conversely, cisplatin led to an increased cell death in the relatively higher oxygen contents because of the cell resistance in hypoxic conditions. The drug testing results showed that it is necessary to take the oxygen tensions in microenvironment into consideration to get a better standing in cellular responses after drug exposure. In summary, the developed microfluidic cell culture device displayed great cell compatibility and gradient controllability, and also provided a useful tool for drug-screening studies with meaningful oxygen tensions in various biomedical applications.

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Acknowledgments

We greatly appreciate the financial support from the Ministry of Science and Technology (2013ZX09507005), National Natural Science Foundation of China (21175080, 21235004, 21475071, 21275082), and Beijing Municipality (Z131100006513009).

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Authors and Affiliations

  1. Collaborative Innovation Center for Marine Biomass Fiber Materials and Textiles, Laboratory of Fiber Materials and Modern Textile, The Growing Base for State Key Laboratory, College of Chemical Science and Engineering, Shandong Sino-Japanese Center for Collaborative Research of Carbon Nanomaterials, Qingdao University, Qingdao, Shandong, 266071, People’s Republic of China

    Zonghua Wang & Zhengxiao Liu

  2. Beijing Key Lab of Microanalytical Methods and Instrumentation, Key Lab of Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing, 100084, People’s Republic of China

    Zhengxiao Liu, Lili Li & Qionglin Liang

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  1. Zonghua Wang
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  2. Zhengxiao Liu
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  3. Lili Li
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  4. Qionglin Liang
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Correspondence to Zonghua Wang or Qionglin Liang.

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Wang, Z., Liu, Z., Li, L. et al. Investigation into the hypoxia-dependent cytotoxicity of anticancer drugs under oxygen gradient in a microfluidic device. Microfluid Nanofluid 19, 1271–1279 (2015). https://doi.org/10.1007/s10404-015-1637-6

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  • DOI: https://doi.org/10.1007/s10404-015-1637-6

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