Gold nanoparticles affect the antioxidant status in selected normal human cells

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 compa...

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Vydáno v:International journal of nanomedicine Ročník 14; s. 4991 - 5015
Hlavní autoři: Daems, Noami, Penninckx, Sébastien, Nelissen, Inge, Van Hoecke, Karen, Cardinaels, Thomas, Baatout, Sarah, Michiels, Carine, Lucas, Stéphane, Aerts, An
Médium: Journal Article
Jazyk:angličtina
Vydáno: New Zealand Dove Medical Press Limited 01.07.2019
Taylor & Francis Ltd
Dove
Dove Medical Press
Témata:
Antibodies
Antioxidants (Nutrients)
Apoptosis
Cancer
Cell growth
Cells (Biology)
Cetuximab
Cysteine
Cystine
Cytotoxicity
EDTA
EGFR
Endothelium
Epidermal growth factors
Gold
Immunotherapy
Kidneys
Kinases
Liver
Monoclonal antibodies
Nanomaterials
Nanoparticles
Nuclear physics
Nuclear research
Original Research
Oxidative stress
Proteins
Targeted cancer therapy
Thioredoxins
United Kingdom
Netherlands
Belgium
France
Germany
United Kingdom > UK
Cetuximab
EGFR
cytotoxicity
oxidative stress
ISSN:1178-2013, 1176-9114, 1178-2013
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Popis
Shrnutí: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). 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. 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.
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ISSN:1178-2013
1176-9114
1178-2013
DOI:10.2147/IJN.S203546