Radiation Enhancer Effect of Platinum Nanoparticles in Breast Cancer Cell Lines: In Vitro and In Silico Analyses
Résumé
Abstract: High‐Z metallic nanoparticles (NPs) are new players in the therapeutic arsenal against
cancer, especially radioresistant cells. Indeed, the presence of these NPs inside malignant cells is
believed to enhance the effect of ionizing radiation by locally increasing the dose deposition. In this
context, the potential of platinum nanoparticles (PtNPs) as radiosensitizers was investigated in two
breast cancer cell lines, T47D and MDA‐MB‐231, showing a different radiation sensitivity. PtNPs
were internalized in the two cell lines and localized in lysosomes and multivesicular bodies. Anal‐
yses of cell responses in terms of clonogenicity, survival, mortality, cell‐cycle distribution, oxidative
stress, and DNA double‐strand breaks did not reveal any significant enhancement effect when cells
were pre‐exposed to PtNPs before being irradiated, as compared to radiation alone. This result is
different from that reported in a previous study performed, under the same conditions, on cervical
cancer HeLa cells. This shows that the efficacy of radio‐enhancement is strongly cell‐type‐depend‐
ent. Simulation of the early stage ionization processes, taking into account the irradiation character‐
istics and realistic physical parameters in the biological sample, indicated that PtNPs could weakly
increase the dose deposition (by 3%) in the immediate vicinity of the nanoparticles. Some features
that are potentially responsible for the biological effect could not be taken into account in the simu‐
lation. Thus, chemical and biological effects could explain this discrepancy. Forinstance, we showed
that, in these breast cancer cell lines, PtNPs exhibited ambivalent redox properties, with an antiox‐
idant potential which could counteract the radio‐enhancement effect. This work shows that the ef‐
ficacy of PtNPs for enhancing radiation effects is strongly cell‐dependent and that no effect is ob‐
served in the case of the breast cancer cell lines T47D and MDA‐MB‐231. Thus, more extensive ex‐
periments using other relevant biological models are needed in order to evaluate such combined
strategies, since several clinical trials have already demonstrated the success of combining
nanoagents with radiotherapy in the treatment of a range of tumor types
Domaines
Sciences du Vivant [q-bio]
Origine : Publication financée par une institution