Amplificazione dell'effetto della dose in radio- e andro- terapia con nanoparticelle d'oro legate a biomarker

Cancer is one of the leading causes of death worldwide. Over 50\% of all patients with localised malignant tumours receive radiotherapy as part of their initial therapy, either alone or in combination with surgery and chemotherapy. The main goal of radiotherapy is the development of an approach offering higher tumour control probability by delivering higher concentrations of dose in the targeted volume whereas sparing as much as possible the surrounding normal tissues. While the quality of the dose conformation is continuously improved by new beam delivery methods, alternative ways to improve the therapy outcome are also being investigated. In recent years, in particular, there has been considerable interest on the use of gold nanoparticles that, thanks to their unique physical and chemical properties, can be exploited in different ways. Radiosensitization in cancerous cells in presence of gold nanoparticles has been demonstrated both \textit{in vitro} and \textit{in vivo} at kilo- and mega- voltage energies, showing promising results. Since gold nanoparticles are easily synthesised and can be designed to interact with various biomolecules, improved diagnosis and treatments efficacy can be obtained by using labeled nanoparticles that target specific cell receptors. In this work a new approach for radiosensitisation, that aims at reaching an understanding of the physical processes occurring in presence of gold nanoparticles bound to biomarkers in both radio- and hadron- therapy, is proposed. Experimental measurements of the concentration of Reactive Oxygen Species (ROS), which are highly reactive molecules that cause biological damage, in the presence of different concentrations of gold nanoparticles are conducted, so as to verify the correlation between ROS and nanoparticles concentration. To have a better understanding of the radiosensitisation processes induced by the presence of gold nanoparticles, a model related to biological outcomes that takes into account the nano-scale deposition of energy through the Local Effect Model (LEM) is also presented. Inhomogeneities in dose deposition that lead to radiosensitisation are introduced by the nanoparticles presence and are here investigated for MDA-MB-231 breast cancer cells containing different sized gold nanoparticles. Results show good agreement between simulations and experimental clonogenic survival assays for both 6 MV and 15 MV X-ray irradiation, suggesting that the model could be used to predict experimental outcomes. Tumour Control Probability (TCP) and Normal Tissue Complication Probability (NTCP) are also evaluated for Planned Target Volumes (PTVs), showing improved results when gold nanoparticles are present.