Modeling gold nanoparticle radiosensitization using a clustering algorithm to quantitate DNA double-strand breaks...

Area of Science:

• Medical Physics
• Nanotechnology
• Radiation Biology

Background:

• Gold nanoparticles (GNPs) are explored for their potential to enhance radiotherapy by increasing radiation-induced DNA damage.
• Accurate modeling is crucial to understand the complex interactions between GNPs, radiation, and cellular structures.

Purpose of the Study:

• To investigate the radiosensitization properties of gold nanoparticles (GNPs) using a detailed Geant4 cell model.
• To characterize DNA double-strand breaks (DSBs) and their correlation with nanoparticle size and proximity to the cell nucleus.

Main Methods:

• A mixed-physics approach combining Geant4-DNA and Livermore physics for simulating low-energy photon interactions.
• Utilized the Density-Based Spatial Clustering of Applications with Noise (DBSCAN) algorithm to quantify DNA DSBs.
• Simulations varied GNP size, distance from the nucleus, and radiation types (80-keV, 100-keV photons, 250-kVp spectrum, 6-MV FFF spectrum).

Main Results:

• GNPs in the cytoplasm significantly enhanced DSB yield and nucleus dose, with effects increasing for larger GNPs and closer proximity to the nucleus.
• GNP distance from the nucleus strongly impacted DSB yield and nucleus dose, but had minimal effect on overall cell dose.
• Observed variable dose and DSB enhancement factors across different radiation energies and GNP configurations.

Conclusions:

• DSB yield is a more sensitive indicator of radiosensitization than cell dose alone, highlighting the importance of evaluating complex radiobiological quantities.
• The nucleus dose closely mirrored DSB yield, validating the model's ability to predict DNA damage and its relationship with nuclear dose.
• The proposed modeling approach aids in understanding GNP radiosensitization mechanisms for improved radiotherapy applications.