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Nanomedicine (Lond). 2018 Nov;13(22):2917-2937. doi: 10.2217/nnm-2018-0171. Epub 2018 Nov 14.

The role of thioredoxin reductase in gold nanoparticle radiosensitization effects.

Author information

1
Research Center for the Physics of Matter & Radiation (PMR-LARN), Namur Research Institute for Life Sciences (NARILIS), University of Namur, Rue de Bruxelles, 61, B-5000 Namur, Belgium.
2
Unité de Recherche en Biologie Cellulaire (URBC), Namur Research Institute for Life Sciences (NARILIS), University of Namur, Rue de Bruxelles 61, B-5000 Namur, Belgium.

Abstract

AIM:

To identify new mechanisms responsible for the radiosensitization effect of gold nanoparticles (GNPs).

MATERIALS & METHODS:

A549 lung carcinoma cells were incubated with 10-nm GNPs during 6 or 24 h before to be exposed to 25 keV/μm protons or 225 kV x-rays.

RESULTS:

GNP incubation led to a time-dependent mitochondria membrane depolarization, oxidative stress and to x-ray and proton radiosensitization. Moreover, a marked inhibition of thioredoxin reductase was observed. Irradiation of cells invalidated for thioredoxin reductase evidenced a radiosensitization effect, suggesting that this enzyme is a potential GNP target.

CONCLUSION:

We suggest that GNPs play a radiosensitizer role by weakening detoxification systems. Altogether, these results open up promising novel strategies for the development of nanotechnologies associated to radiotherapy.

KEYWORDS:

biological mechanism; gold nanoparticles; proton irradiation; radiosensitization; thioredoxin reductase

PMID:
30427254
DOI:
10.2217/nnm-2018-0171

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