Impact of the hypoxic phenotype on the uptake and efflux of nanoparticles by human breast cancer cells

Abstract Breast cancer cells adapt to the hypoxic tumoral environment by undergoing changes in metabolism, cell signalling, endo-lysosomal receptor uptake and recycling. The resulting hypoxic cell phenotype has the potential to undermine the therapeutic efficacy of nanomedicines designed for endocyt...

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Autores principales:	William J. Brownlee, F. Philipp Seib
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9c9e13b623684df89ce2382f99d10d94
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spelling	oai:doaj.org-article:9c9e13b623684df89ce2382f99d10d942021-12-02T11:41:14ZImpact of the hypoxic phenotype on the uptake and efflux of nanoparticles by human breast cancer cells10.1038/s41598-018-30517-32045-2322https://doaj.org/article/9c9e13b623684df89ce2382f99d10d942018-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-30517-3https://doaj.org/toc/2045-2322Abstract Breast cancer cells adapt to the hypoxic tumoral environment by undergoing changes in metabolism, cell signalling, endo-lysosomal receptor uptake and recycling. The resulting hypoxic cell phenotype has the potential to undermine the therapeutic efficacy of nanomedicines designed for endocytic uptake and specific intracellular trafficking. The aim of this study was to examine the impact of hypoxia and simulated reperfusion on the in vitro uptake and release of nanomedicines by human breast cancer cells. Cells were exposed to a hypoxic preconditioning treatment in 1% oxygen for 6 and 24 hours to induce temporal changes in the hypoxic circuit (e.g. HIF-1α expression). The preconditioned cells were then dosed with nanoparticles for 45 or 180 minutes emulating nanomedicine access following tumor reperfusion. Hypoxic preconditioning significantly increased nanoparticle retention by up to 10% when compared to normoxic cultures, with the greatest relative difference between normoxic and hypoxic cultures occurring with a 45 minute dosing interval. Exocytosis studies indicated that the preconditioned cells had a significantly increased nanoparticle efflux (up to 9%) when compared to normoxic cells. Overall, we were able to show that hypoxic preconditioning regulates both the endocytosis and exocytosis of nanomedicines in human breast cancer cells.William J. BrownleeF. Philipp SeibNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-11 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q William J. Brownlee F. Philipp Seib Impact of the hypoxic phenotype on the uptake and efflux of nanoparticles by human breast cancer cells
description	Abstract Breast cancer cells adapt to the hypoxic tumoral environment by undergoing changes in metabolism, cell signalling, endo-lysosomal receptor uptake and recycling. The resulting hypoxic cell phenotype has the potential to undermine the therapeutic efficacy of nanomedicines designed for endocytic uptake and specific intracellular trafficking. The aim of this study was to examine the impact of hypoxia and simulated reperfusion on the in vitro uptake and release of nanomedicines by human breast cancer cells. Cells were exposed to a hypoxic preconditioning treatment in 1% oxygen for 6 and 24 hours to induce temporal changes in the hypoxic circuit (e.g. HIF-1α expression). The preconditioned cells were then dosed with nanoparticles for 45 or 180 minutes emulating nanomedicine access following tumor reperfusion. Hypoxic preconditioning significantly increased nanoparticle retention by up to 10% when compared to normoxic cultures, with the greatest relative difference between normoxic and hypoxic cultures occurring with a 45 minute dosing interval. Exocytosis studies indicated that the preconditioned cells had a significantly increased nanoparticle efflux (up to 9%) when compared to normoxic cells. Overall, we were able to show that hypoxic preconditioning regulates both the endocytosis and exocytosis of nanomedicines in human breast cancer cells.
format	article
author	William J. Brownlee F. Philipp Seib
author_facet	William J. Brownlee F. Philipp Seib
author_sort	William J. Brownlee
title	Impact of the hypoxic phenotype on the uptake and efflux of nanoparticles by human breast cancer cells
title_short	Impact of the hypoxic phenotype on the uptake and efflux of nanoparticles by human breast cancer cells
title_full	Impact of the hypoxic phenotype on the uptake and efflux of nanoparticles by human breast cancer cells
title_fullStr	Impact of the hypoxic phenotype on the uptake and efflux of nanoparticles by human breast cancer cells
title_full_unstemmed	Impact of the hypoxic phenotype on the uptake and efflux of nanoparticles by human breast cancer cells
title_sort	impact of the hypoxic phenotype on the uptake and efflux of nanoparticles by human breast cancer cells
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/9c9e13b623684df89ce2382f99d10d94
work_keys_str_mv	AT williamjbrownlee impactofthehypoxicphenotypeontheuptakeandeffluxofnanoparticlesbyhumanbreastcancercells AT fphilippseib impactofthehypoxicphenotypeontheuptakeandeffluxofnanoparticlesbyhumanbreastcancercells
_version_	1718395415154393088

Impact of the hypoxic phenotype on the uptake and efflux of nanoparticles by human breast cancer cells

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