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Sensors 2017, 17(12), 2827; https://doi.org/10.3390/s17122827

Co-Cultured Continuously Bioluminescent Human Cells as Bioreporters for the Detection of Prodrug Therapeutic Impact Pre- and Post-Metabolism

1
Center for Environmental Biotechnology, The University of Tennessee, Knoxville, TN 37996, USA
2
490 BioTech, Inc., Knoxville, TN 37996, USA
3
Entomology Department, Cornell University, Ithaca, NY 14850, USA
*
Author to whom correspondence should be addressed.
Received: 20 October 2017 / Revised: 1 December 2017 / Accepted: 2 December 2017 / Published: 6 December 2017
(This article belongs to the Special Issue Novel Sensors for Bioimaging)
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Abstract

Modern drug discovery workflows require assay systems capable of replicating the complex interactions of multiple tissue types, but that can still function under high throughput conditions. In this work, we evaluate the use of substrate-free autobioluminescence in human cell lines to support the performance of these assays with reduced economical and logistical restrictions relative to substrate-requiring bioluminescent reporter systems. The use of autobioluminescence was found to support assay functionality similar to existing luciferase reporter targets. The autobioluminescent assay format was observed to correlate strongly with general metabolic activity markers such as ATP content and the presence of reactive oxygen species, but not with secondary markers such as glutathione depletion. At the transcriptional level, autobioluminescent dynamics were most closely associated with expression of the CYP1A1 phase I detoxification pathway. These results suggest constitutively autobioluminescent cells can function as general metabolic activity bioreporters, while pairing expression of the autobioluminescent phenotype to detoxification pathway specific promoters could create more specific sensor systems. View Full-Text
Keywords: bioluminescence; bacterial luciferase; pharmaceutical development; optical imaging bioluminescence; bacterial luciferase; pharmaceutical development; optical imaging
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Xu, T.; Conway, M.; Frank, A.; Ripp, S.; Sayler, G.; Close, D. Co-Cultured Continuously Bioluminescent Human Cells as Bioreporters for the Detection of Prodrug Therapeutic Impact Pre- and Post-Metabolism. Sensors 2017, 17, 2827.

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