Integrating Gold Nanoparticles with Brachytherapy: In Vitro Insights into Radiosensitization in Cervical Cancer.

Background/Objectives: Cervical cancer treatment relies heavily on high-dose-rate (HDR) 192Ir brachytherapy; however, therapeutic efficacy remains limited by tumor radioresistance and the inability to escalate dose without increasing toxicity to surrounding healthy tissues. The present study investigates the potential of gold nanoparticles (AuNPs) to enhance radiosensitivity under clinically relevant 192Ir brachytherapy conditions through the combined action of physical dose amplification and radiobiological modulation. Particular emphasis is placed on the unique radiophysical interactions generated by the mixed gamma and secondary beta emissions of 192Ir, which, in the presence of high atomic number nanoparticles, promote localized photoelectric absorption and the emission of low-range secondary electrons, including Auger electrons. The study further aims to determine how AuNPs size and post-irradiation temporal evolution influence radiation-induced cytotoxicity and apoptosis in cervical cancer cell lines, thereby providing a biologically representative model of nanoparticle-assisted brachytherapy. Methods: Clonogenic survival, dose enhancement factor (DEF), and apoptosis were evaluated following irradiation in the presence of 10 nm and 50 nm AuNPs in two independent biological experiments (n = 2). Results: A clear dose-dependent reduction in survival fraction and increase in apoptosis were observed in nanoparticle-treated groups compared with irradiation alone. Radiosensitization demonstrated strong size dependence, with 50 nm AuNPs producing the greatest enhancement, a finding that may reflect size-dependent differences in cellular internalization, intracellular distribution, and nanoscale energy deposition previously established in AuNP studies. Importantly, biological effects intensified at later post-irradiation intervals, demonstrating a sustained temporal evolution of the radiobiological response beyond the initial irradiation event, potentially involving oxidative and other delayed cellular stress mechanisms described in AuNP radiosensitization. Conclusions: These findings demonstrate the capacity of AuNPs to enhance the radiobiological response of cervical cancer cells to 192Ir brachytherapy and identify nanoparticle size and post-irradiation time as important determinants of this effect. They therefore support AuNP-assisted brachytherapy as a promising strategy for further development toward biologically optimized radiotherapy capable of improving tumor response without escalation of the prescribed radiation dose.