Ponente
Descripción
In the recent years, proton-therapy has become one of the most researched techniques for irradiating tumours. This technique implies a clinical advantage over conventional photon therapies due to the unique depth-dose characteristics of protons, which can be exploited to target the tumoral cells while reducing the dose delivered to the healthy tissues. On the other hand, photothermal therapy (PTT) is a minimally invasive local treatment modality whose goal is to convert eletromagnetic radiation into heat by stimulation of photoabsorbing agents that are administrated to the body either intravenously or intratumorally. Laser light in the near-infrared (NIR) region (700-1100 nm) is the energy source used in PTT due to the higher tissue penetration capability and lower absorption in biological tissues [1]. Among several molecules and nanomaterials used, gold nanostructures have been extensively explored as photothermal agents due to their biocompatibility and ability to generate heat due to the absorption of electromagnetic radiation [1].
The strong photoelectric absorption coefficient of gold, the high-Z of this element, combined with high Auger and Coster–Kronig (C-K) electron emission yields, make the gold nanoparticles excellent radiosensitizers, offering local radiation dose enhancement of up to 200% [2] [3]. Recent studies have also evaluated this effect when proton-therapy is used in combination with the nanoparticles. Experimental studies using proton beams in cell lines have showed enhanced responses in the cells with internalized gold nanoparticles. The radiosensitizing effect of gold nanoparticles was studied for proton, megavoltage (MV) photon and kilovoltage (kV) photon beams. For each particle source, various treatment depths were achieved. The cell viability was significantly reduced for both proton and MV photon irradiations when nanoparticles were internalized in the cell, reaching a sensitizer enhancement ratio between 1.33 and 3.98 depending on the nanoparticles concentration and internalization by the cells [4]. The results of using the nanoparticles as radiosensitizers in proton therapy are promising, however, the possibility of combining proton and photo therapies must be explored.
In this work we will present our most recent experiments at CMAM to study the synergy between photothermia and proton-therapy. First, several concentrations of gold nanoparticles in liquid were irradiated with a proton beam to evaluate the temperature evolution depending on the laser power [5]: (i) during the proton beam irradiation and (ii) after the proton beam irradiation to evaluate the impact of the proton beam irradiation in the photothermal behaviour. We observed a significant increase in the temperature and seems to indicate a synergic effect between proton and laser irradiation. Then glioblastoma multiform cells (U87mg) with and without internalized gold nanoparticles were also irradiated with several doses and proton beam intensities. The cell viability was evaluated after irradiation using Alamar Blue and clonogenic essays. We will also determine the reactive oxygen species (ROS) produced after laser and proton irradiation and the cell cycle by flow cytometry to explore the causes of cell death. In addition to experiments, we study the charge transfer and ionization processes in proton-uracil collisions, in the energy range of 0.05 < E < 2500 keV [6], in order to build a simple model that allow us to obtain inelastic cross sections from molecular orbital energies. Some efforts to the description of the molecular fragmentation after proton impact are also carried out within the group [7].
