Nikolaos Kollaros

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.

Background/Objectives: Proton therapy provides superior dose conformity and better normal tissue sparing than conventional radiotherapy but is limited by its relatively low relative biological effectiveness (RBE). Nanoparticles have emerged as promising proton radiosensitizers capable of enhancing physical dose deposition and biological responses. Methods: A narrative literature review was conducted using PubMed, Scopus, Web of Science, and Google Scholar. Results: Gold nanoparticles were the most extensively studied radiosensitizers, while platinum, gadolinium, hafnium oxide, titanium dioxide, iron oxide, and other nanoparticles also demonstrated promising radiosensitizing effects. Evidence indicates that nanoparticles enhance local dose deposition, increase LET and ROS production, promote DNA damage, and improve tumor control. Conclusions: Nanoparticle-assisted proton therapy represents a promising strategy for improving cancer treatment by increasing therapeutic efficacy while preserving healthy tissues. Although preclinical studies demonstrate significant improvements in therapeutic efficacy, challenges related to tumor targeting, biodistribution, safety, and clinical validation remain. Further research is required to facilitate clinical implementation.

The aim of this study was to evaluate knowledge-based treatment planning (KBP) models in terms of their dosimetry and deliverability and to investigate their clinical benefits. Three H&N KBP models were built utilizing RapidPlan™, based on the dose prescription, which is given according to the planning target volume (PTV). The training set for each model consisted of 43 clinically acceptable volumetric modulated arc therapy (VMAT) plans. Model quality was assessed and compared to the delivered treatment plans using the homogeneity index (HI), conformity index (CI), structure dose difference (PTV, organ at risk—OAR), monitor units, MU factor, and complexity index. Model deliverability was assessed through a patient-specific quality assurance (PSQA) gamma index-based analysis. The dosimetric assessment showed better OAR sparing for the RapidPlan™ plans and for the low- and high-risk PTV, and the HI, and CI were comparable between the clinical and RapidPlan™ plans, while for the intermediate-risk PTV, CI was better for clinical plans. The 2D gamma passing rates for RapidPlan™ plans were similar or better than the clinical ones using the 3%/3 mm gamma-index criterion. Monitor units, the MU factors, and complexity indices were found to be comparable between RapidPlan™ and the clinical plans. Knowledge-based treatment plans can be safely adapted into clinical routines, providing improved plan quality in a time efficient way while minimizing user variability.