Reducing Tumour Hypoxia via Oral Administration of Oxygen Nanobubbles.

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 oral...

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Main Authors: Joshua Owen, Conor McEwan, Heather Nesbitt, Phurit Bovornchutichai, Raymond Averre, Mark Borden, Anthony P McHale, John F Callan, Eleanor Stride
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2016-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0168088&type=printable
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author Joshua Owen
Conor McEwan
Heather Nesbitt
Phurit Bovornchutichai
Raymond Averre
Mark Borden
Anthony P McHale
John F Callan
Eleanor Stride
author_facet Joshua Owen
Conor McEwan
Heather Nesbitt
Phurit Bovornchutichai
Raymond Averre
Mark Borden
Anthony P McHale
John F Callan
Eleanor Stride
author_sort Joshua Owen
collection DOAJ
description 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 hypoxia-inducible-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).
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spelling doaj-art-b5f4e39f1fe145db8a8595a12febe9382025-08-20T03:26:10ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-011112e016808810.1371/journal.pone.0168088Reducing Tumour Hypoxia via Oral Administration of Oxygen Nanobubbles.Joshua OwenConor McEwanHeather NesbittPhurit BovornchutichaiRaymond AverreMark BordenAnthony P McHaleJohn F CallanEleanor StrideHypoxia 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 hypoxia-inducible-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).https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0168088&type=printable
spellingShingle Joshua Owen
Conor McEwan
Heather Nesbitt
Phurit Bovornchutichai
Raymond Averre
Mark Borden
Anthony P McHale
John F Callan
Eleanor Stride
Reducing Tumour Hypoxia via Oral Administration of Oxygen Nanobubbles.
PLoS ONE
title Reducing Tumour Hypoxia via Oral Administration of Oxygen Nanobubbles.
title_full Reducing Tumour Hypoxia via Oral Administration of Oxygen Nanobubbles.
title_fullStr Reducing Tumour Hypoxia via Oral Administration of Oxygen Nanobubbles.
title_full_unstemmed Reducing Tumour Hypoxia via Oral Administration of Oxygen Nanobubbles.
title_short Reducing Tumour Hypoxia via Oral Administration of Oxygen Nanobubbles.
title_sort reducing tumour hypoxia via oral administration of oxygen nanobubbles
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0168088&type=printable
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