A multi-scale Monte Carlo simulation on nanoparticle dose enhancement for a lung tumour treated with low-energy brachytherapy.

Low-energy brachytherapy using ¹²⁵I and ¹⁰³Pd seeds offers an effective treatment strategy for lung tumours by maximizing tumour dose delivery while sparing adjacent healthy tissues. It has been shown that the addition of metal nanoparticles (NPs) in the tumour can improve the treatment outcomes in radiotherapy. This study investigates the dose enhancement potential of gold (Au), platinum (Pt), and bismuth (Bi) NPs at concentrations of 3 and 7 mg/g through multi-scale Monte Carlo simulations using Geant4 (macroscopic) and Geant4-DNA (microscopic) toolkits. Results demonstrate consistent dose enhancement ratios (DERs) of up to 2.6 across both scales, with Bi NPs showing superior performance than Au and Pt NPs, due to their higher atomic number. DNA damage increased proportionally with NP concentration, confirming their radio-sensitizing potential. Furthermore, indirect free radical-mediated DNA damage accounted for ~ 90% of total damage, demonstrating the critical role of chemical-stage effects in NP radio-sensitization. The strong correlation between macroscopic and microscopic findings validates Bi NPs as optimal enhancers for low-energy lung brachytherapy, particularly when combined with ¹²⁵I seeds. These results provide a robust foundation for clinical translation of NP-augmented brachytherapy protocols.