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\subsection{Abstract}  \textbf{Purpose/objective}: In recent years there has been considerable interest in the use of gold nanoparticles (GNPs) combined with radiotherapy to improve tumor control. It has been demonstrated how the presence of GNPs significantly enhance cells radiosensitization. Furthermore,  GNPs exhibit unique physical and chemical properties and can be designed to bindto  molecules that target specific cell receptors, resulting which could result  in improved diagnosis and treatments efficacy. However, a quantification of the expected clinical improvements is still lacking. In this work a new approach for estimating the improved nanoparticle-driven radiosensitivity is presented and a quantification of the treatment optimality as a function of GNP GNPs  uptake is performed. \textbf{Materials and Methods}: In order to assess the biological effects, a stochastic radiobiological model derived from the Local Effect Model (LEM) approach was coupled with Monte Carlo simulations performed using Geant4, so as to estimate the local dose deposited by secondary electrons atthe  nanometric level. A closed analytical formulation of the model was also derived for MV irradiation. The model was benchmarked for MDA-MB-231 breast cancer cells containing different concentrations of GNPs and then used to investigate breast cancer cases for planned treatments with both 6 MV and 15 MV photons. Treatment simulations of 6 patients were performed at each energy, in which a parametrization of the GNPs uptake with varying tumor selectivity was introduced. The expected treatment optimality as a function of the spatially varying gold uptake was quantified in terms of Tumor Control Probability (TCP) and Normal Tissue Complication Probability (NTCP). \textbf{Results}: Results show good agreement between simulations and experimental clonogenic survival assays for both 6 MV and 15 MV, suggesting that the model could be used to predict experimental outcomes in a clinical setup. The breast Breast  cancer simulations show improved treatment outcomes when GNPs bound to targeting agents are present. For %For  all treatments, with 3 Gy per fraction and 13 fractions (START A) and 2.67 Gy with 15 fractions (START B), B) [8],  a maximum TCP increase of 20\% was observed in the 6 MV case, assuming a maximum concentration of 12 uM GNP in the tumoral region. \textbf{Conclusions}: A model to account for GNPs uptake and tissue radiosensitization was implemented and included in the simulation of breast cancer treatments. In addition to the improved treatment efficacy, the possibility of a short course of fractionation in combination with GNPs was also investigated.  \textbf{Conclusions}: A model to account for GNP uptake and tissue radiosentitization was implemented and included in the simulation of breast cancer treatments. In addition to the improved treatment efficacy, the possibility of a short course of fractionation in combination with GNP was also quantified.