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

Research output: Contribution to journal › Article › peer-review

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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.

Original language	English
Pages (from-to)	2917-2937
Number of pages	21
Journal	Nanomedicine
Volume	13
Issue number	22
DOIs	https://doi.org/10.2217/nnm-2018-0171
Publication status	Published - 1 Nov 2018

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.2217/nnm-2018-0171

nnm-2018-0171-penninckx2018Licence: Unspecified

Cite this

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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,

day = "1",

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

language = "English",

volume = "13",

pages = "2917--2937",

journal = "Nanomedicine",

issn = "1743-5889",

publisher = "Future Medicine Ltd.",

number = "22",

}

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.

KW - biological mechanism

KW - gold nanoparticles

KW - proton irradiation

KW - radiosensitization

KW - thioredoxin reductase

KW - Protons

KW - A549 Cells

KW - Radiation-Sensitizing Agents/metabolism

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

UR - https://www.futuremedicine.com/doi/10.2217/nnm-2018-0171

UR - http://www.mendeley.com/research/role-thioredoxin-reductase-gold-nanoparticle-radiosensitization-effects

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U2 - 10.2217/nnm-2018-0171

DO - 10.2217/nnm-2018-0171

M3 - Article

C2 - 30427254

SN - 1743-5889

VL - 13

SP - 2917

EP - 2937

JO - Nanomedicine

JF - Nanomedicine

IS - 22

ER -

The role of thioredoxin reductase in gold nanoparticle radiosensitization effects

Abstract

Keywords

UN SDGs

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Other files and links

Fingerprint

Advances in the Mechanistic Understanding of Iron Oxide Nanoparticles' Radiosensitizing Properties

PROTHER-WAL: Proton Therapy Research in Wallonia

Flow Cytometry

Morphology - Imaging

Synthesis, Irradiation and Analysis of Materials (SIAM)

Cite this

The role of thioredoxin reductase in gold nanoparticle radiosensitization effects

Abstract

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Research output

Advances in the Mechanistic Understanding of Iron Oxide Nanoparticles' Radiosensitizing Properties

Projects

PROTHER-WAL: Proton Therapy Research in Wallonia

Equipment

Flow Cytometry

Morphology - Imaging

Synthesis, Irradiation and Analysis of Materials (SIAM)

Cite this