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. 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.
Highlights
Introduction conditions of the Creative CommonsAmong the therapeutic strategies available to combat solid tumors, radiotherapy (RT)is used in more than half of cases
This first in vivo demonstration paved the way for a growing number of publications, which indicates the potential of high-Z nanoparticles in terms of enhancing the ionizing radiation effect
The platinum nanoparticles (PtNPs) uptake was characterized after exposure of two different breast cancer cell lines, T47D and MDA-MB-231
Summary
Introduction conditions of the Creative CommonsAmong the therapeutic strategies available to combat solid tumors, radiotherapy (RT)is used in more than half of cases. Directly induce nucleic acid strand breaks, but it can produce free radicals by water radiolysis These species contribute to DNA damage, leading to cell death, depending on the cancer cell radiation sensitivity [1]. Research on radiotherapy currently focuses on increasing the dose and dose rate delivered to a tumor with a better ballistic for preserving healthy tissues Concerning the latter point, the use of metallic high-Z nanoparticles (NPs) seems very promising for enhancing the radiation effect within a tumor, as the photoelectric interaction cross-section is dependent on Z5. In a mouse mammary carcinoma model, Hainfeld et al [2] showed a clear radio-sensitization effect of gold nanoparticles delivered to tumors before irradiation This first in vivo demonstration paved the way for a growing number of publications, which indicates the potential of high-Z nanoparticles in terms of enhancing the ionizing radiation effect. Gold, gadolinium, and hafnium nanoparticles are mainly studied [1]
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