Unravelling the Mechanism of Gold Nanoparticle Radiosensitization in protontherapy

To compensate for the limitations of conventional radiotherapy, the
treatment of cancer patients with medical fast ion beams is growing, driven
by their particular physical properties. Recently, a number of studies have
shown the ability to improve the therapeutic effect by using metallic
nanoparticles. In this context, we want to unravel the mechanisms
responsible for the enhancement of gold nanoparticle radiosensitization
effect. The current theory predicts that the interaction between the beam
and these nanoparticles leads to the formation of radical oxygen species
(ROS), amongst others. These unstable chemical species would cause
additional DNA damage. Nevertheless, in the light of latest research carried
out in our laboratory, it seems unlikely that this nanoparticle - beam
interaction alone cannot explain the radiosensitization effect. In this context,
we approach this research project from two different perspectives. Firstly,
we study the nature of ROS formed during irradiation and determine
whether or not the incident particle, the dose rate and / or the linear energy
transfer influence the formation of these ROS in both their nature and their
concentration. On the other hand, we study the nanoparticles effect on cells
without irradiation in order to investigate the induction of metabolic changes
within them. These alterations can amplify the biological effects of radiation
and / or impact DNA repair processes. By combining all the results, we
hope to determine the mechanisms responsible for the increase in cell
death when nanoparticles are present. This thesis will contribute to the
improvement of the physics of hadrontherapy treatments and will optimize
the chances of curability of cancer patients.