Abstract
To identify new mechanisms responsible for the radiosensitization effect of gold nanoparticles (GNPs). A549 lung carcinoma cells were incubated with 10-nm GNPs during 6 or 24h before to be exposed to 25keV/μm protons or 225kV x-rays. 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. 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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