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Engineering a Brain Cancer Chip for High-throughput Drug Screening

Glioblastoma multiforme (GBM) is the most common and malignant of all human primary brain cancers, in which drug treatment is still one of the most effective treatments. However, existing drug discovery and development methods rely on the use of conventional two-dimensional (2D) cell cultures, which...

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Autores principales: Fan, Yantao, Nguyen, Duong Thanh, Akay, Yasemin, Xu, Feng, Akay, Metin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4858657/
https://www.ncbi.nlm.nih.gov/pubmed/27151082
http://dx.doi.org/10.1038/srep25062
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author Fan, Yantao
Nguyen, Duong Thanh
Akay, Yasemin
Xu, Feng
Akay, Metin
author_facet Fan, Yantao
Nguyen, Duong Thanh
Akay, Yasemin
Xu, Feng
Akay, Metin
author_sort Fan, Yantao
collection PubMed
description Glioblastoma multiforme (GBM) is the most common and malignant of all human primary brain cancers, in which drug treatment is still one of the most effective treatments. However, existing drug discovery and development methods rely on the use of conventional two-dimensional (2D) cell cultures, which have been proven to be poor representatives of native physiology. Here, we developed a novel three-dimensional (3D) brain cancer chip composed of photo-polymerizable poly(ethylene) glycol diacrylate (PEGDA) hydrogel for drug screening. This chip can be produced after a few seconds of photolithography and requires no silicon wafer, replica molding, and plasma bonding like microfluidic devices made of poly(dimethylsiloxane) (PDMS). We then cultured glioblastoma cells (U87), which formed 3D brain cancer tissues on the chip, and used the GBM chip to perform combinatorial treatment of Pitavastatin and Irinotecan. The results indicate that this chip is capable of high-throughput GBM cancer spheroids formation, multiple-simultaneous drug administration, and a massive parallel testing of drug response. Our approach is easily reproducible, and this chip has the potential to be a powerful platform in cases such as high-throughput drug screening and prolonged drug release. The chip is also commercially promising for other clinical applications, including 3D cell culture and micro-scale tissue engineering.
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spelling pubmed-48586572016-05-19 Engineering a Brain Cancer Chip for High-throughput Drug Screening Fan, Yantao Nguyen, Duong Thanh Akay, Yasemin Xu, Feng Akay, Metin Sci Rep Article Glioblastoma multiforme (GBM) is the most common and malignant of all human primary brain cancers, in which drug treatment is still one of the most effective treatments. However, existing drug discovery and development methods rely on the use of conventional two-dimensional (2D) cell cultures, which have been proven to be poor representatives of native physiology. Here, we developed a novel three-dimensional (3D) brain cancer chip composed of photo-polymerizable poly(ethylene) glycol diacrylate (PEGDA) hydrogel for drug screening. This chip can be produced after a few seconds of photolithography and requires no silicon wafer, replica molding, and plasma bonding like microfluidic devices made of poly(dimethylsiloxane) (PDMS). We then cultured glioblastoma cells (U87), which formed 3D brain cancer tissues on the chip, and used the GBM chip to perform combinatorial treatment of Pitavastatin and Irinotecan. The results indicate that this chip is capable of high-throughput GBM cancer spheroids formation, multiple-simultaneous drug administration, and a massive parallel testing of drug response. Our approach is easily reproducible, and this chip has the potential to be a powerful platform in cases such as high-throughput drug screening and prolonged drug release. The chip is also commercially promising for other clinical applications, including 3D cell culture and micro-scale tissue engineering. Nature Publishing Group 2016-05-06 /pmc/articles/PMC4858657/ /pubmed/27151082 http://dx.doi.org/10.1038/srep25062 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Fan, Yantao
Nguyen, Duong Thanh
Akay, Yasemin
Xu, Feng
Akay, Metin
Engineering a Brain Cancer Chip for High-throughput Drug Screening
title Engineering a Brain Cancer Chip for High-throughput Drug Screening
title_full Engineering a Brain Cancer Chip for High-throughput Drug Screening
title_fullStr Engineering a Brain Cancer Chip for High-throughput Drug Screening
title_full_unstemmed Engineering a Brain Cancer Chip for High-throughput Drug Screening
title_short Engineering a Brain Cancer Chip for High-throughput Drug Screening
title_sort engineering a brain cancer chip for high-throughput drug screening
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4858657/
https://www.ncbi.nlm.nih.gov/pubmed/27151082
http://dx.doi.org/10.1038/srep25062
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