Evaluation of Synergistic Radiosensitization Using Gold Nanoparticles and paclitaxel for HDR Brachytherapy In 2D and 3D Prostate Cancer Models
Abstract
Purpose
To investigate the synergistic radiosensitization of gold nanoparticles (GNPs) and paclitaxel (PTX) in high dose-rate (HDR) brachytherapy for prostate cancer using 2D (monolayer) and 3D (spheroid) cell models. HDR is used as a localized boost following external beam radiation to achieve final tumor control. While effective, further reducing radiation-induced toxicity in surrounding normal tissue remains a priority. This study investigates a unique combination of radiosensitizing agents, GNP+PTX, to enhance the localized physical dose without increasing the prescribed radiation.
Methods
PC3 prostate cancer cells were treated with GNPs (10μg/mL) and PTX (4 nM) in monolayer and spheroid conditions. Samples were irradiated (0-5 Gy) using an 192Ir source and a custom Solid Water phantom. GNP uptake and retention were quantified via ICP-MS and hyperspectral imaging. Monolayer models were evaluated using clonogenic assays and DNA double-strand break assays, while relative growth of spheroids were tracked post-irradiation.
Results
24-hour GNP uptake was similar between groups (5.2 x 10⁵ GNPs/cell), however GNP+PTX treated cells showed significantly higher gold retention at 48 hours (p < 0.05) compared to GNP treated cells. At 2 Gy, the surviving fraction was reduced by 22% (p < 0.05) for the combined GNP+PTX treatment compared to GNP treatment alone. In spheroid models, preliminary trials showed the combination of GNP+PTX resulted in the greatest growth inhibition at 2 Gy, restricting growth to 147% of the initial volume, whereas the PTX-only and control groups restricted growth by 172% and 300% of their initial volumes, respectively.
Conclusion
Dual administration of GNPs and PTX enhanced therapeutic outcomes in both monolayer and spheroid models. The spheroid results demonstrate treatment efficacy within realistic tumor architectures and oxygen gradients, enabling a more reliable translation to clinical practice. This combination treatment demonstrates high potential for sparing normal tissue while improving tumor control in clinical HDR brachytherapy.