The role of thioredoxin reductase in gold nanoparticle radiosensitization effects

Research output: Contribution to journalArticle

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 languageEnglish
Pages (from-to)2917-2937
Number of pages21
JournalNanomedicine
Volume13
Issue number22
Early online date2018
DOIs
Publication statusPublished - 1 Nov 2018
Externally publishedYes

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

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  • Equipment

  • Morphology - Imaging

    Charles Nicaise (Manager) & Francesca Cecchet (Manager)

    Technological Platform Morphology - Imaging

    Facility/equipment: Technological Platform

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