Metallic nanoparticles are promising agents for increasing the effectiveness of radiation therapy by making cells more sensitive to radiation. High atomic number nanoparticles generate low-energy secondary electrons that initiate a cascade of physical and chemical reactions, which can lead to enhanced cell damage and tumor control. However, despite the growing interest in this area, a comprehensive understanding of the biological consequences of these reactions remains elusive due to the lack of experimental data. To address this gap, the Geant4-DNA track structure code has been used for modeling the interactions of radiation with matter at the molecular and cellular levels. The Geant4-DNA track structure code an extension of the Geant4 simulation toolkit designed for modeling the interactions of radiation with biological systems with high precision. Since the Geant4-DNA code is broadly applied for radiosensitization simulations, the authors were motivated to conduct a review of the literature and provide a comprehensive information on the current status of nanoparticle radiosensitization simulations using Geant4-DNA.

This review aims to analyze and categorize the existing knowledge, identify key findings, research gaps, and challenges, and provide recommendations for future research in this area. A comprehensive search for the articles that used Geant4-DNA for nanoparticle radiosensitization was performed. A total of 50 studies met the inclusion criteria, and their simulation data and major findings are extracted. According to the literature, despite the significant contribution of the Geant4-DNA code, validating simulation results against experimental data is a primary challenge because there are limited experimental studies available. In addition, detailed modeling of nanoparticle radiosensitization require an accurate depiction of the cellular microenvironment and incorporation of chemical and biological reactions, which, in turn, demands the utilization of high-performance computers. Our analysis of the literature also reveals that most current studies are focused on gold nanoparticles with cellular distribution, and photon or proton radiations. This could emphasize the need for future research to consider other potential metallic nanoparticles in combination with various particle irradiations as well as utilization of high performance computers.