The role of thioredoxin reductase in gold nanoparticle radiosensitization effects

Sébastien Penninckx; Anne-Catherine Heuskin; Carine Michiels; Stéphane Lucas

doi:10.2217/nnm-2018-0171

The role of thioredoxin reductase in gold nanoparticle radiosensitization effects

Sébastien Penninckx, Anne-Catherine Heuskin, Carine Michiels, Stéphane Lucas

Résultats de recherche: Contribution à un journal/une revue › Article › Revue par des pairs

Résumé

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.

langue originale	Anglais
Pages (de - à)	2917-2937
Nombre de pages	21
journal	Nanomedicine
Volume	13
Numéro de publication	22
Date de mise en ligne précoce	2018
Les DOIs	https://doi.org/10.2217/nnm-2018-0171
Etat de la publication	Publié - 1 nov. 2018
Modification externe	Oui

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Contient cette citation

@article{962fedd34fd8484fbec03ea287af307c,

title = "The role of thioredoxin reductase in gold nanoparticle radiosensitization effects",

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, Protons, A549 Cells, Radiation-Sensitizing Agents/metabolism, Humans, Metal Nanoparticles/chemistry, Gold/chemistry, Oxidative Stress/drug effects, Particle Size, X-Rays, Surface Properties, DNA Damage/drug effects, Cell Proliferation/drug effects, Radiotherapy/methods, Thioredoxin-Disulfide Reductase/metabolism",

author = "S{\'e}bastien Penninckx and Anne-Catherine Heuskin and Carine Michiels and St{\'e}phane Lucas",

year = "2018",

month = nov,

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doi = "10.2217/nnm-2018-0171",

language = "English",

volume = "13",

pages = "2917--2937",

journal = "Nanomedicine",

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TY - JOUR

T1 - The role of thioredoxin reductase in gold nanoparticle radiosensitization effects

AU - Penninckx, Sébastien

AU - Heuskin, Anne-Catherine

AU - Michiels, Carine

AU - Lucas, Stéphane

PY - 2018/11/1

Y1 - 2018/11/1

N2 - 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.

AB - 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.

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KW - thioredoxin reductase

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KW - Humans

KW - Metal Nanoparticles/chemistry

KW - Gold/chemistry

KW - Oxidative Stress/drug effects

KW - Particle Size

KW - X-Rays

KW - Surface Properties

KW - DNA Damage/drug effects

KW - Cell Proliferation/drug effects

KW - Radiotherapy/methods

KW - Thioredoxin-Disulfide Reductase/metabolism

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The role of thioredoxin reductase in gold nanoparticle radiosensitization effects

Résumé

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FACS

Morphologie - Imagerie

Synthèse, Irradiation et Analyse de Matériaux (SIAM)

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