Journal
NANOMEDICINE
Volume 14, Issue 16, Pages 2209-2226Publisher
FUTURE MEDICINE LTD
DOI: 10.2217/nnm-2019-0086
Keywords
3D hepatocyte chip; nanotoxicology; superparamagnetic iron oxide nanoparticles (SPION); primary rat hepatocytes; albumin; urea
Funding
- China Scholarship Council
- National Natural Science Foundation of China [31770107, 21874116]
- Scientific and Technological Research Council of Turkey (TUBITAK)
- National Institutes of Health [1R21EB020192, 5R01EB023812, 5P41EB002503]
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Aim: To develop a practical microfluidic 3D hepatocyte chip for hepatotoxicity testing of nanoparticles using proof of concept studies providing first results of the potential hepatotoxicity of superparamagnetic iron oxide nanoparticles (SPION) under microfluidic conditions. Methods: A microfluidic 3D hepatocyte chip with three material layers, which contains primary rat hepatocytes, has been fabricated and tested using different concentrations (50, 100 and 200 mu g/ml) of SPION in 3-day (short-term) and 1-week (long-term) cultures. Results: Compared with standard well plates, the hepatocyte chip with flow provided comparable viability and significantly higher liver-specific functions, up to 1 week. In addition, the chip recapitulates the key physiological responses in the hepatotoxicity of SPION. Conclusion: Thus, the developed 3D hepatocyte chip is a robust and highly sensitive platform for investigating hepatotoxicity profiles of nanoparticles.
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