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\section{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. GNPs exhibit unique physical and chemical properties and can be designed to bind to molecules that target specific cell receptors, resulting 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 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 at the 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).