Study of the intracellular nanoparticle-based radiosensitization mechanisms in F98 glioma cells treated with charged particle therapy through synchrotron-based infrared microspectroscopy
Résumé
The use of nanoparticles (NP) as dose enhancers in radiotherapy (RT) is a growing research field. Recently,
the use of NP has been extended to charged particle therapy in order to improve the performance in
radioresistant tumors. However, the biological mechanisms underlying the synergistic effects involved in
NP-RT approaches are not clearly understood. Here, we used the capabilities of synchrotron-based
Fourier Transform Infrared Microspectroscopy (SR-FTIRM) as a bio-analytical tool to elucidate the NPinduced cellular damage at the molecular level and at a single-cell scale. F98 glioma cells doped with
AuNP and GdNP were irradiated using several types of medical ion beams (proton, helium, carbon and
oxygen). Differences in cell composition were analyzed in the nucleic acids, protein and lipid spectral
regions using multivariate methods (Principal Component Analysis, PCA). Several NP-induced cellular
modifications were detected, such as conformational changes in secondary protein structures, intensity
variations in the lipid CHx stretching bands, as well as complex DNA rearrangements following charged
particle therapy irradiations. These spectral features seem to be correlated with the already shown
enhancement both in the DNA damage response and in the reactive oxygen species (ROS) production by
the NP, which causes cell damage in the form of protein, lipid, and/or DNA oxidations. Vibrational features
were NP-dependent due to the NP heterogeneous radiosensitization capability. Our results provided new
insights into the molecular changes in response to NP-based RT treatments using ion beams, and highlighted the relevance of SR-FTIRM as a useful and precise technique for assessing cell response to innovative radiotherapy approaches.
Domaines
Physique [physics]
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