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Article Dans Une Revue International Journal of Molecular Sciences Année : 2021

Radiation Enhancer Effect of Platinum Nanoparticles in Breast Cancer Cell Lines: In Vitro and In Silico Analyses

Marie Hullo
  • Fonction : Auteur
LCE
Romain Grall
  • Fonction : Auteur
LCE
Cécile Mathe
  • Fonction : Auteur
LCE
Véronique Menard
  • Fonction : Auteur
LCE
Xiaomin Yang
Erika Porcel
Emmanuelle Bourneuf
  • Fonction : Auteur
LCE

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
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hal-03550120 , version 1 (31-01-2022)

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Marie Hullo, Romain Grall, Yann Perrot, Cécile Mathe, Véronique Menard, et al.. Radiation Enhancer Effect of Platinum Nanoparticles in Breast Cancer Cell Lines: In Vitro and In Silico Analyses. International Journal of Molecular Sciences, 2021, 22, pp.4436. ⟨10.3390/ijms22094436⟩. ⟨hal-03550120⟩
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