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Reducing Tumour Hypoxia via Oral Administration of Oxygen Nanobubbles

Owen, Joshua, McEwan, Conor, Nesbitt, Heather, Bovornchutichai, Phurit, Averre, Raymond, Borden, Mark, McHale, Anthony, Callan, John F and Stride, Eelanor (2016) Reducing Tumour Hypoxia via Oral Administration of Oxygen Nanobubbles. PLOS ONE, 11 (12). e0168088. [Journal article]

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DOI: 10.1371/journal.pone.0168088

Abstract

Hypoxia has been shown to be a key factor inhibiting the successful treatment of solid tumours. Existing strategies for reducing hypoxia, however, have shown limited efficacy and/or adverse side effects. The aim of this study was to investigate the potential for reducing tumour hypoxia using an orally delivered suspension of surfactant-stabilised oxygen nanobubbles. Experiments were carried out in a mouse xenograft tumour model for human pancreatic cancer (BxPc-3 cells in male SCID mice). A single dose of 100 μL of oxygen saturated water, oxygen nanobubbles or argon nanobubbles was administered via gavage. Animals were sacrificed 30 minutes post-treatment (3 per group) and expression of hypoxiainducible-factor-1α (HIF1α) protein measured by real time quantitative polymerase chain reaction and Western blot analysis of the excised tumour tissue. Neither the oxygen saturated water nor argon nanobubbles produced a statistically significant change in HIF1α expression at the transcriptional level. In contrast, a reduction of 75% and 25% in the transcriptional and translational expression of HIF1α respectively (p<0.001) was found for the animals receiving the oxygen nanobubbles. This magnitude of reduction has been shown in previous studies to be commensurate with an improvement in outcome with both radiation and drug-based treatments. In addition, there was a significant reduction in the expression of vascular endothelial growth factor (VEGF) in this group and corresponding increase in the expression of arrest-defective protein 1 homolog A (ARD1A).

Item Type:Journal article
Keywords:Nanobubbles, Oxygen, Hypoxia, HIF-1 alpha
Faculties and Schools:Faculty of Life and Health Sciences > School of Pharmacy and Pharmaceutical Science
Faculty of Life and Health Sciences > School of Biomedical Sciences
Faculty of Life and Health Sciences
Research Institutes and Groups:Biomedical Sciences Research Institute > Genomic Medicine
Biomedical Sciences Research Institute
Biomedical Sciences Research Institute > Pharmacy & Pharmaceutical Sciences
ID Code:37069
Deposited By: Professor John Callan
Deposited On:06 Mar 2017 09:09
Last Modified:12 Sep 2017 13:23

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