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Résumé

Purpose: 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.

langue originaleAnglais
Pages (de - à)4991-5015
Nombre de pages25
journalNanomedicine
Volume14
Les DOIs
étatPublié - 1 janv. 2019

Empreinte digitale

Cytotoxicity
Antioxidants
Gold
Nanoparticles
Cells
Depolarization
Cell death
Epidermal Growth Factor Receptor
Membranes
Oxidative stress
Endothelial cells
Antibodies
Liver
Tissue
Apoptosis
Thioredoxin-Disulfide Reductase
Glutathione Reductase
Mitochondrial Membrane Potential
Acetylcysteine
Mitochondrial Membranes

Citer ceci

@article{4b80392e5a6243b6b52f73313eea3c22,
title = "Gold nanoparticles affect the antioxidant status in selected normal human cells",
abstract = "Purpose: 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",
author = "Noami Daems and S{\'e}bastien Penninckx and Inge Nelissen and {Van Hoecke}, Karen and Thomas Cardinaels and Sarah Baatout and Carine Michiels and St{\'e}phane Lucas and An Aerts",
year = "2019",
month = "1",
day = "1",
doi = "10.2147/IJN.S203546",
language = "English",
volume = "14",
pages = "4991--5015",
journal = "Nanomedicine",
issn = "1743-5889",
publisher = "Future Medicine Ltd.",

}

Gold nanoparticles affect the antioxidant status in selected normal human cells. / Daems, Noami; Penninckx, Sébastien; Nelissen, Inge; Van Hoecke, Karen; Cardinaels, Thomas; Baatout, Sarah; Michiels, Carine; Lucas, Stéphane; Aerts, An.

Dans: Nanomedicine, Vol 14, 01.01.2019, p. 4991-5015.

Résultats de recherche: Contribution à un journal/une revueArticle

TY - JOUR

T1 - Gold nanoparticles affect the antioxidant status in selected normal human cells

AU - Daems, Noami

AU - Penninckx, Sébastien

AU - Nelissen, Inge

AU - Van Hoecke, Karen

AU - Cardinaels, Thomas

AU - Baatout, Sarah

AU - Michiels, Carine

AU - Lucas, Stéphane

AU - Aerts, An

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Purpose: 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.

AB - Purpose: 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.

KW - Cytotoxicity

KW - EGFR

KW - Cetuximab

KW - Oxidative stress

UR - http://www.scopus.com/inward/record.url?scp=85070990002&partnerID=8YFLogxK

U2 - 10.2147/IJN.S203546

DO - 10.2147/IJN.S203546

M3 - Article

VL - 14

SP - 4991

EP - 5015

JO - Nanomedicine

JF - Nanomedicine

SN - 1743-5889

ER -