Gold nanoparticles affect the antioxidant status in selected normal human cells

Noami Daems,1 Sébastien Penninckx,2 Inge Nelissen,3 Karen Van Hoecke,4 Thomas Cardinaels,4,5 Sarah Baatout,1 Carine Michiels,6 Stéphane Lucas,2 An Aerts11Radiobiology Research Unit, Interdisciplinary Biosciences, Institute for Environment, Health and Safety, Belgian Nu...

Full description

Bibliographic Details
Main Authors: Daems N, Penninckx S, Nelissen I, Van Hoecke K, Cardinaels T, Baatout S, Michiels C, Lucas S, Aerts A
Format: Article
Language:English
Published: Dove Medical Press 2019-07-01
Series:International Journal of Nanomedicine
Subjects:
Online Access:https://www.dovepress.com/gold-nanoparticles-affect-the-antioxidant-status-in-selected-normal-hu-peer-reviewed-article-IJN
_version_ 1831570235864383488
author Daems N
Penninckx S
Nelissen I
Van Hoecke K
Cardinaels T
Baatout S
Michiels C
Lucas S
Aerts A
author_facet Daems N
Penninckx S
Nelissen I
Van Hoecke K
Cardinaels T
Baatout S
Michiels C
Lucas S
Aerts A
author_sort Daems N
collection DOAJ
description Noami Daems,1 Sébastien Penninckx,2 Inge Nelissen,3 Karen Van Hoecke,4 Thomas Cardinaels,4,5 Sarah Baatout,1 Carine Michiels,6 Stéphane Lucas,2 An Aerts11Radiobiology Research Unit, Interdisciplinary Biosciences, Institute for Environment, Health and Safety, Belgian Nuclear Research Centre (SCK.CEN), Mol, Belgium; 2Research Center for the Physics of Matter and Radiation-NARILIS, University of Namur, Namur, Belgium; 3Health Department, Flemish Institute For Technological Research (VITO), Mol, Belgium; 4Radiochemistry Expert Group, Institute for Nuclear Materials Science, Belgian Nuclear Research Centre (SCK.CEN), Mol, Belgium; 5Department of Chemistry, KU Leuven, Heverlee, Belgium; 6Unité de Recherche en Biologie Cellulaire-NARILIS, University of Namur, Namur, BelgiumPurpose: This study evaluates the cytotoxicity of AuNPs coated with polyallylamine (AuNPs-PAA) and conjugated or not to the epidermal growth factor receptor (EGFR)-targeting antibody Cetuximab (AuNPs-PAA-Ctxb) in normal human kidney (HK-2), liver (THLE-2) and microvascular endothelial (TIME) cells, and compares it with two cancer cell lines that are EGFR-overexpressing (A431) or EGFR-negative (MDA-MB-453).Results: Conjugation of Cetuximab to AuNPs-PAA increased the AuNPs-PAA-Ctxb interactions with cells, but reduced their cytotoxicity. TIME cells exhibited the strongest reduction in viability after exposure to AuNPs-PAA(±Ctxb), followed by THLE-2, MDA-MB-453, HK-2 and A431 cells. This cell type-dependent sensitivity was strongly correlated to the inhibition of thioredoxin reductase (TrxR) and glutathione reductase (GR), and to the depolarization of the mitochondrial membrane potential. Both are suggested to initiate apoptosis, which was indeed detected in a concentration- and time-dependent manner. The role of oxidative stress in AuNPs-PAA(±Ctxb)-induced cytotoxicity was demonstrated by co-incubation of the cells with N-acetyl L-cysteine (NAC), which significantly decreased apoptosis and mitochondrial membrane depolarization.Conclusion: This study helps to identify the cells and tissues that could be sensitive to AuNPs and deepens the understanding of the risks associated with the use of AuNPs in vivo.Keywords: cytotoxicity, EGFR, Cetuximab, oxidative stress
first_indexed 2024-12-17T12:47:39Z
format Article
id doaj.art-20c81d3974c548d0b171ef40fafafd89
institution Directory Open Access Journal
issn 1178-2013
language English
last_indexed 2024-12-17T12:47:39Z
publishDate 2019-07-01
publisher Dove Medical Press
record_format Article
series International Journal of Nanomedicine
spelling doaj.art-20c81d3974c548d0b171ef40fafafd892022-12-21T21:47:41ZengDove Medical PressInternational Journal of Nanomedicine1178-20132019-07-01Volume 144991501546937Gold nanoparticles affect the antioxidant status in selected normal human cellsDaems NPenninckx SNelissen IVan Hoecke KCardinaels TBaatout SMichiels CLucas SAerts ANoami Daems,1 Sébastien Penninckx,2 Inge Nelissen,3 Karen Van Hoecke,4 Thomas Cardinaels,4,5 Sarah Baatout,1 Carine Michiels,6 Stéphane Lucas,2 An Aerts11Radiobiology Research Unit, Interdisciplinary Biosciences, Institute for Environment, Health and Safety, Belgian Nuclear Research Centre (SCK.CEN), Mol, Belgium; 2Research Center for the Physics of Matter and Radiation-NARILIS, University of Namur, Namur, Belgium; 3Health Department, Flemish Institute For Technological Research (VITO), Mol, Belgium; 4Radiochemistry Expert Group, Institute for Nuclear Materials Science, Belgian Nuclear Research Centre (SCK.CEN), Mol, Belgium; 5Department of Chemistry, KU Leuven, Heverlee, Belgium; 6Unité de Recherche en Biologie Cellulaire-NARILIS, University of Namur, Namur, BelgiumPurpose: This study evaluates the cytotoxicity of AuNPs coated with polyallylamine (AuNPs-PAA) and conjugated or not to the epidermal growth factor receptor (EGFR)-targeting antibody Cetuximab (AuNPs-PAA-Ctxb) in normal human kidney (HK-2), liver (THLE-2) and microvascular endothelial (TIME) cells, and compares it with two cancer cell lines that are EGFR-overexpressing (A431) or EGFR-negative (MDA-MB-453).Results: Conjugation of Cetuximab to AuNPs-PAA increased the AuNPs-PAA-Ctxb interactions with cells, but reduced their cytotoxicity. TIME cells exhibited the strongest reduction in viability after exposure to AuNPs-PAA(±Ctxb), followed by THLE-2, MDA-MB-453, HK-2 and A431 cells. This cell type-dependent sensitivity was strongly correlated to the inhibition of thioredoxin reductase (TrxR) and glutathione reductase (GR), and to the depolarization of the mitochondrial membrane potential. Both are suggested to initiate apoptosis, which was indeed detected in a concentration- and time-dependent manner. The role of oxidative stress in AuNPs-PAA(±Ctxb)-induced cytotoxicity was demonstrated by co-incubation of the cells with N-acetyl L-cysteine (NAC), which significantly decreased apoptosis and mitochondrial membrane depolarization.Conclusion: This study helps to identify the cells and tissues that could be sensitive to AuNPs and deepens the understanding of the risks associated with the use of AuNPs in vivo.Keywords: cytotoxicity, EGFR, Cetuximab, oxidative stresshttps://www.dovepress.com/gold-nanoparticles-affect-the-antioxidant-status-in-selected-normal-hu-peer-reviewed-article-IJNcytotoxicityEGFRCetuximaboxidative stress
spellingShingle Daems N
Penninckx S
Nelissen I
Van Hoecke K
Cardinaels T
Baatout S
Michiels C
Lucas S
Aerts A
Gold nanoparticles affect the antioxidant status in selected normal human cells
International Journal of Nanomedicine
cytotoxicity
EGFR
Cetuximab
oxidative stress
title Gold nanoparticles affect the antioxidant status in selected normal human cells
title_full Gold nanoparticles affect the antioxidant status in selected normal human cells
title_fullStr Gold nanoparticles affect the antioxidant status in selected normal human cells
title_full_unstemmed Gold nanoparticles affect the antioxidant status in selected normal human cells
title_short Gold nanoparticles affect the antioxidant status in selected normal human cells
title_sort gold nanoparticles affect the antioxidant status in selected normal human cells
topic cytotoxicity
EGFR
Cetuximab
oxidative stress
url https://www.dovepress.com/gold-nanoparticles-affect-the-antioxidant-status-in-selected-normal-hu-peer-reviewed-article-IJN
work_keys_str_mv AT daemsn goldnanoparticlesaffecttheantioxidantstatusinselectednormalhumancells
AT penninckxs goldnanoparticlesaffecttheantioxidantstatusinselectednormalhumancells
AT nelisseni goldnanoparticlesaffecttheantioxidantstatusinselectednormalhumancells
AT vanhoeckek goldnanoparticlesaffecttheantioxidantstatusinselectednormalhumancells
AT cardinaelst goldnanoparticlesaffecttheantioxidantstatusinselectednormalhumancells
AT baatouts goldnanoparticlesaffecttheantioxidantstatusinselectednormalhumancells
AT michielsc goldnanoparticlesaffecttheantioxidantstatusinselectednormalhumancells
AT lucass goldnanoparticlesaffecttheantioxidantstatusinselectednormalhumancells
AT aertsa goldnanoparticlesaffecttheantioxidantstatusinselectednormalhumancells