Radiotherapeutic efficacy of gold nanoparticles for high dose-rate brachytherapy compared to conventional radiotherapy: An in vitro study

Background: Radiation therapy is a pivotal part of the treatment plan for many cancer patients. Effective dose escalation in the tumour is required to achieve optimal curative results but is hindered by normal tissue toxicity. Gold nanoparticles (GNPs) as radiosensitizers to improve the radiation cross-section of malignant tissue is one avenue currently being explored to improve therapeutic results. It is hypothesized that at lower incident photon energies, dose enhancement from GNPs should be significantly greater compared to high-energy irradiations due to a greater photoelectric cross-section. Purpose: To assess GNP radiosensitization in vitro during low-energy, high-dose-rate brachytherapy (HDR-BT) irradiations and compare to the measured radiosensitization from a 6MV photon beam from a clinical linear accelerator (LINAC). Methods: A novel Solid Water Phantom was developed for uniform irradiations from a common HDR-BT source (192-Ir) and verified using EBT-4 radiochromic film. HeLa (cervical) and PC3 (prostate) monolayer cell cultures were used to represent common HDR-BT treatment sites. The cells were dosed at 10 mu g/mL concentration with functionalized 12 nm spherical GNPs. GNP uptake in the cellular membrane was quantified using live-cell imaging and a trace element analysis technique. Cell cultures with or without GNPs were irradiated from the 192-Ir source or clinical 6 MV photon beam from a LINAC to a 200 cGy dose prescription. Cellular viability was measured using a clonogenic assay and DNA double-strand break (DSB) assay. Results: Endocytosis of spherical GNPs was confirmed 24 h post-incubation, resulting in an average of 8.7 x 10(5) GNPs/cell and 6.0 x 10(5) GNPs/cell for HeLa and PC3 cell cultures, respectively. The incorporation of GNPs induced 183% (p < 0.001) and 364% (p = 0.01) greater DNA DSBs with HDR-BT irradiations compared to LINAC irradiations for HeLa and PC3 cells, respectively, after the 200 cGy prescription. GNPs reduced the survival fraction of HeLa and PC3 cells after 2 weeks post-irradiation by 4.6% (p < 0.05) and 8.5% (p < 0.05), respectively, with HDR irradiations compared to LINAC irradiations. Conclusions: Our results suggest GNP incorporation into HDR-BT is a viable and effective treatment strategy. As our dosing concentration in this study induced no measurable cellular toxicity, this strategy has the potential to be implemented in clinical scenarios. Ultimately, we believe that incorporating GNPs into radiotherapy workflows can increase radiotherapeutic efficacy, improving the quality of life for cancer patients.