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Photoactivation of Iron Nanoparticles for the Improvement of Glioma Treatment

By Solveig Reymond, Paul Gimenez, Mélanie Flaender, Rachel Delorme, C. Bissardon, J-K Kim, Sylvain Bohic, J. Arnaud, Raphaël Serduc, Jean-Luc Ravanat and Hélène Elleaume

Abstract

International audienceRationale : An alternative approach for the improvement of radiotherapy consists in increasing differentially the radiation dose between tumors and normal tissues using nanoparticles (NPs) that have been beforehand internalized into the tumor. These high-Z NPs can be photo-activated by monochromatic synchrotron X-rays, leading to a local dose enhancement delivered to the neighbouring tumor cells. In this study, we evaluated the ability of iron NPs to act as radiosensitizers in vitro and through simulations.Materials and Methods : The radiosensitizing effect of Fe NPs was assessed through Monte Carlo simulations (PENELOPE) and in vitro experiments: F98 tumor cells were incubated for 24h with Fe NPs before being irradiated at 30 keV, 51 keV or 80 keV. The cell survival was measured by clonogenicity and MTT assays. Subsequently, the iron intake after a 24h incubation with NPs was characterized using ICP-MS and the iron distribution was studied thanks to X-ray fluorescence microscopy.Results : F98 are able to endocytose NPs: we measured ~20±4pg of internalized iron per cell (initial iron concentration: 0.06mg/mL in culture medium). The Fe NPs are located in vacuoles in the cytoplasm. The presence of Fe NPs in the cells caused a 1.6±0.4 enhancement of cell death with 30 keV irradiation (initial iron concentrations in culture medium 0.06 mg/mL).Conclusion : F98 tumor cells were able to endocytose and retain Fe NPs in their cytoplasm, and a significative effect of the NPs was observed for a 30 keV irradiation. Our following studies will attempt to better characterize and optimize the radio-sensitizer properties of Fe NPs and shed light on another way to distribute them into the tumor site.This work was supported by the LabEx PRIMES Lyon, France. We thank ESRF for the beamtime and technical support

Topics: nanoparticle, dose enhancement, radiotherapy, [PHYS.PHYS.PHYS-MED-PH]Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], [SDV.CAN]Life Sciences [q-bio]/Cancer
Publisher: HAL CCSD
Year: 2018
OAI identifier: oai:HAL:hal-01990774v1
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