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

Research output: Contribution to journalArticle

1 Citation (Scopus)

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 MDA-MB-231 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. Pericellular oxygen monitoring indicated oxygen tension declined exponentially to 2.3% within 30 minutes and 1.3% within 60 minutes. 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.
LanguageEnglish
Article number12318
Number of pages11
JournalScientific Reports
Volume8
Early online date17 Aug 2018
DOIs
Publication statusE-pub ahead of print - 17 Aug 2018

Fingerprint

Nanoparticles
Breast Neoplasms
Phenotype
Nanomedicine
Exocytosis
Oxygen
Reperfusion
Hypoxia
Recycling
Endocytosis

Keywords

  • hypoxia
  • nanomedicine
  • endocytosis
  • exocytosis
  • HIF1

Cite this

@article{258702af69df4fbba0954ecebc73136d,
title = "Impact of the hypoxia 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 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 MDA-MB-231 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. Pericellular oxygen monitoring indicated oxygen tension declined exponentially to 2.3{\%} within 30 minutes and 1.3{\%} within 60 minutes. 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.",
keywords = "hypoxia, nanomedicine, endocytosis, exocytosis, HIF1",
author = "Brownlee, {William J.} and Seib, {F. Philipp}",
year = "2018",
month = "8",
day = "17",
doi = "10.1038/s41598-018-30517-3",
language = "English",
volume = "8",
journal = "Scientific Reports",
issn = "2045-2322",

}

TY - JOUR

T1 - Impact of the hypoxia phenotype on the uptake and efflux of nanoparticles by human breast cancer cells

AU - Brownlee, William J.

AU - Seib, F. Philipp

PY - 2018/8/17

Y1 - 2018/8/17

N2 - 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 MDA-MB-231 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. Pericellular oxygen monitoring indicated oxygen tension declined exponentially to 2.3% within 30 minutes and 1.3% within 60 minutes. 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.

AB - 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 MDA-MB-231 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. Pericellular oxygen monitoring indicated oxygen tension declined exponentially to 2.3% within 30 minutes and 1.3% within 60 minutes. 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.

KW - hypoxia

KW - nanomedicine

KW - endocytosis

KW - exocytosis

KW - HIF1

UR - https://nature.com/srep/

U2 - 10.1038/s41598-018-30517-3

DO - 10.1038/s41598-018-30517-3

M3 - Article

VL - 8

JO - Scientific Reports

T2 - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 12318

ER -