Exploring the Potential of Gold Nanoparticles in Proton Therapy: Mechanisms, Advances, and Clinical Horizons
Giorgio Giuseppe Carbone, Stefania Mariano, Alessandra Gabriele, Sabrina Cennamo, Vitantonio Primiceri, Muhammad Rizwan Aziz, Elisa Panzarini, Lucio Calcagnile
Abstract
Proton therapy represents a groundbreaking advancement in cancer radiotherapy, leveraging the unique spatial energy distribution of protons to deliver precise, high-dose radiation to tumors while sparing surrounding healthy tissues. Despite its clinical success, proton therapy faces challenges in optimizing its therapeutic precision and efficacy. Recent research has highlighted the potential of gold nanoparticles to enhance proton therapy outcomes. Due to their high atomic number and favorable biological properties, gold nanoparticles act as radiosensitizers by amplifying the generation of secondary electrons and reactive oxygen species upon proton irradiation. This enhances DNA damage in tumor cells while preserving healthy tissues. Additionally, functionalization of gold nanoparticles with tumor-targeting ligands offers improved precision, making proton therapy more effective against a broader range of cancers. This review synthesizes current knowledge on the mechanisms of gold nanoparticle radiosensitization, preclinical evidence, and the technological hurdles that must be addressed to integrate this promising approach into clinical practice, aiming to advance the efficacy and accessibility of proton therapy in cancer therapy.