Gold nanoparticles affect the antioxidant status in selected normal human cells

Noami Daems, Sébastien Penninckx, Inge Nelissen, Karen Van Hoecke, Thomas Cardinaels, Sarah Baatout, Carine Michiels, Stéphane Lucas, An Aerts

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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.

Original languageEnglish
Pages (from-to)4991-5015
Number of pages25
JournalNanomedicine
Volume14
DOIs
Publication statusPublished - 1 Jan 2019

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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

Keywords

  • Cytotoxicity
  • EGFR
  • Cetuximab
  • Oxidative stress

Cite this

Daems, N., Penninckx, S., Nelissen, I., Van Hoecke, K., Cardinaels, T., Baatout, S., ... Aerts, A. (2019). Gold nanoparticles affect the antioxidant status in selected normal human cells. Nanomedicine, 14, 4991-5015. https://doi.org/10.2147/IJN.S203546
Daems, Noami ; Penninckx, Sébastien ; Nelissen, Inge ; Van Hoecke, Karen ; Cardinaels, Thomas ; Baatout, Sarah ; Michiels, Carine ; Lucas, Stéphane ; Aerts, An. / Gold nanoparticles affect the antioxidant status in selected normal human cells. In: Nanomedicine. 2019 ; Vol. 14. pp. 4991-5015.
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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.

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

Research output: Contribution to journalArticle

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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

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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.

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