Leal Plaza, Antonio2024-09-272024-09-272024-03-20López Valverde, J.A. (2024). Feasibility Evaluation of the Use of Gold Nanoparticles as Theragnostic Agents for Personalized and Precision Radiotherapy. (Tesis Doctoral Inédita). Universidad de Sevilla, Sevilla.https://hdl.handle.net/11441/162991Gold nanoparticles arouse a special interest in radiotherapy. Multiple studies have already shown their potential use as diagnostic and therapeutic agents. In diagnostics they can be used as contrast agents, while in therapy they could act as dose enhancers and radiosensitizers. The purpose of this study is to synthesize and characterize a nanoparticle formulation for this application, to explore the possibilities of gold nanoparticles as theragnostic agents under clinical conditions, to assess the radiosensitization provided in this scenario, and to settle the base scenario for a later phase of preclinical experimentation with animal models. Gold nanoparticles were firstly synthesized with a bottom-up chemical approach and later commercially acquired, and all of them were characterized. They were tested as contrast agents under realistic clinical conditions in both CT scanners and megavoltage cone-beam CT (MV-CBCT) scanners for image-guided radiotherapy. The dose enhancement benefit of these nanoparticles under different conditions and their dependence on critical parameters was evaluated. Furthermore, their therapeutical performance was assessed in optimization treatment planning of actual clinical cases, by virtualizing the presence of nanoparticles in the tumor target considering an efficient targeting. Moreover, gold nanoparticles dose enhancement experimental verification was attempted. Additionally, the radiosensitization effect was evaluated using immunofluorescence and cytogenetic in vitro experimentation, and a model of the associated radiosensitization was proposed using TOPAS and TOPAS-nBio code. Lastly, the bases were settled for future animal experimentation. Gold nanoparticles performed successfully in a theragnostic scenario under the clinical conditions of MVCBCT incidence beam over not deep tumors such as head and neck and breast cancer cases. A concentration around 20 mg Au/mL inside the tumor volume, in combination with this energy beam, showed a dose enhancement superior to the 15% and radiosensitization of more than 45%.application/pdf198 P.engAttribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/openAccess