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

International Journal of Molecular Sciences

Emmanuelle Bourneuf¹  Cécile Mathé¹  Sylvie Chevillard¹  Marie Hullo¹  Véronique Ménard¹  Romain Grall¹  Carmen Villagrasa²  Yann Perrot²  Xiaomin Yang³  Erika Porcel³  Sandrine Lacombe³ 

[1] Commissariat à l’Energie Atomique et aux Energies Alternatives (CEA), Fundamental Research Division (DRF), François Jacob Institute (IBFJ), Institute of Molecular and Cellular Radiobiology (IRCM), Laboratoire de Cancérologie Expérimentale (LCE), University Paris Saclay, Route du Panorama, CEDEX, 92265 Fontenay-aux-Roses, France;IRSN, Institut de Radioprotection et de Sûreté Nucléaire, BP17, 92962 Fontenay-aux-Roses, France;Institut des Sciences Moléculaires d’Orsay, Université Paris Saclay, CNRS UMR 8214, 91405 Orsay, France;

关键词: platinum nanoparticle;    ionizing radiation;    dose enhancement effect;    radiation enhancement effect;    radiation sensitivity;    radiation resistance;   

DOI  :  10.3390/ijms22094436

来源: DOAJ

【 摘 要 】

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. Analyses 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-dependent. Simulation of the early stage ionization processes, taking into account the irradiation characteristics 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 simulation. Thus, chemical and biological effects could explain this discrepancy. For instance, we showed that, in these breast cancer cell lines, PtNPs exhibited ambivalent redox properties, with an antioxidant potential which could counteract the radio-enhancement effect. This work shows that the efficacy of PtNPs for enhancing radiation effects is strongly cell-dependent and that no effect is observed in the case of the breast cancer cell lines T47D and MDA-MB-231. Thus, more extensive experiments 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.

【 授权许可】

Unknown