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\section{Introduction}
The goal of radiotherapy is that of delivering the highest damage (\textit{i.e.}, the highest dose) to the tumor volume while simultaneously sparing the surrounding healthy tissues. In recent years there has been considerable interest on the use of nanoparticles as novel agents for cancer therapy, with many studies in diverse fields including preclinical and clinical trials \cite{Zhang_2008,Rahman_2009,Cao_Mil_n_2014}. In particular, radiosensitization in cancerous cells in presence of gold nano particles (GNP) has been demonstrated both \textit{in vitro} and \textit{in vivo} at kilo- and mega- voltage energies energies \cite{Hainfeld_2004,Kong_2008,Rahman_2009,Jain_2012}
The high radiosensitization induced at kilovoltage energies by gold nanoparticles is well documented by both \textit{in vitro} and \textit{in vivo} studies (mice with implanted tumors) \cite{Hainfeld_2004}\cite{Kong_2008}[Rah09, Jai12]. As an example, irradiation of cells loaded with gold foils reported dose enhancement factors higher than 100 [Reg98, Reg02]. As the concentration of nanoparticles increases the radiosensitization increases [Rah09, Lec13, Ran10], probably due to the higher number of photoelectric interactions and consequently higher dose deposition as well as an additional oxidative stress induced by the presence of nanoparticles [Pan09, Kan10]. Experimental studies have revealed that gold nanoparticles radiosensitization are also highly sensitive to photon source energy [Chi10, Asg10], cancer cell type [Pat07, Jai11], nanoparticle size [But12] and their localization relative to cellular DNA [Bru09].
The premise of GNP radiosensitization relies on gold’s increased photoelectric absorption cross-section relative to tissue. As a consequence the radiosensitization observed at kilovoltage energies by increased photoabsorption cannot help predict the effects occurring at clinically relevant megavoltage energies, where Compton interactions are dominant and photon energy absorption weakly depends on the atomic number. Ionization rates at megavoltage energies seem to be extremely low, meaning that, for doses typically used in radiotherapy, a fair amount of nanoparticles present in the system (i.e., more than 99\%) does not contribute to the dose deposition processes. However, despite this minimal dose increase, it is worth noticing that the presence of gold nanoparticles do lead to significant levels of radiosensitization. This must therefore be dependent on factors other than strong photoelectric absorption, such as different distributions of energy deposition compared to those in soft tissues and/or additional oxidative stress induced by the presence of nanoparticles [Pan09, Kan10]. In particular, as it will be later discussed, it was found that only one ionization from the nanoparticles is necessary to lead the cell to its demise.
