Simulation Study on Effects of Gold Nanoparticle Size and Concentration on Radiation Sensitization

Radiotherapy stands as a cornerstone in cancer treatment, where a critical challenge in treatment planning involves maximizing the local tumor control probability while minimizing radiation-induced damage to surrounding healthy tissues. Radiosensitizers, which enhance the therapeutic ratio, have emerged as a viable strategy to improve radiotherapy efficacy. Gold nanoparticles (GNP), as novel high atomic number (Z=79) nanomaterials, demonstrate exceptional potential in radiation sensitization owing to their superior biocompatibility, low toxicity, and mature synthesis methodologies. Experimental studies confirm that GNP embedded in biological tissues amplify radiation-induced cellular damage, thereby achieving radiation sensitization. Consequently, micro/nanoscale dosimetric investigations of GNP-mediated radiation effects hold significant clinical value for advancing precision radiotherapy. In this study, the Geant4-DNA Monte Carlo simulation toolkit was employed to develop a simplified spherical cell model, comprising a nucleus, cytoplasm, and GNP, to investigate GNP-induced radiation sensitization. The cytoplasm was modeled as liquid water to reflect its 70%-80% aqueous composition. The radiation dose enhancement factor (DEF), defined as the ratio of absorbed doses in cells or nuclei under identical irradiation conditions with and without GNP, was utilized to quantify radiation sensitization. Based on biological evidence indicating predominant cytoplasmic localization of GNP with minimal nuclear uptake, simulations incorporated two GNP spatial distributions within the cytoplasm: uniform and random configurations. The DEF values in the nucleus were calculated across varying incident photon energies. Key findings reveal that GNP significantly enhance intracellular radiation doses at 200 keV (DEF＞1), while exhibiting slight dose attenuation (DEF＜1) at 280 keV and 300 keV. At higher energies (≥250 keV), GNPs show negligible effects (DEF≈1). Comparative analysis with prior studies by Xie et al. demonstrated consistency at 70 keV and 100 keV but discrepancies at other energies, potentially attributable to differences between the microscopic correction model used here and the macroscopic interaction model adopted in their work. Furthermore, GNP size-dependent analysis identified 74 nm as the optimal diameter for maximal sensitization. Concentration-dependent studies reveal a linear positive correlation between DEF and GNP concentration (0.01-20 mg/mL) in both the nucleus and cytoplasm. By systematically quantifying the interplay of GNP size, concentration, and photon energy on DEF, this study elucidates the nanoscale mechanisms underlying GNP-mediated radiation sensitization. The results provide a theoretical foundation for optimizing clinical parameters, including GNP size selection (74 nm), concentration thresholds, and energy tuning (200 keV), to maximize therapeutic efficacy while mitigating toxicity. These insights advance the development of precision radiotherapy protocols integrating GNPs as next-generation radiosensitizers.