Efficacy of Gold Nanoparticles for High Dose Rate Brachytherapy: An In Vitro and in vivo Study
Abstract
Purpose
Gold nanoparticles (GNPs) are promising radiosensitizing agents for high dose rate brachytherapy (HDR); however, complex treatment delivery for HDR has prohibited systematic evaluation of GNP-induced radiosensitization both in vitro and in vivo. Here, we use in-house built water equivalent phantoms and irradiation platforms to determine the radiotherapeutic efficacy of GNPs both in vitro and in vivo for HDR.
Methods
In vitro experiments were conducted on a prostate cancer cell line (PC3) in both 2D monolayer and 3D spheroids, dosed at 10μg/mL. In vivo, PC3 tumour bearing male NRG mice were intratumourally injected with functionalized GNPs at 2mg/kg bodyweight. GNPs were functionalized with polyethylene glycol (GNPPEG) or with integrin binding domain RGD (GNPPEG-RGD). Irradiations were conducted using a clinical HDR-BT afterloader. Monolayer cell survival was quantified using the clonogenic (0 - 8 Gy) and DNA damage assay (2 Gy). Spheroid growth was used determine efficacy in 3D (4 Gy). Tumour growth and bodyweight change post-irradiation to 400cGy was evaluated in vivo to determine the efficacy of the GNP platforms.
Results
In vitro and in vivo, GNPPEG did not elicit any measurable radiosensitization. In vitro, GNPPEG-RGD elicited a loss in clonogenic survival of 17% (p=0.001) and an increase in DNA damage of 33% (p=0.005). Spheroid growth was also stunted by 57% (p<0.0001). In vivo, tumour growth was significantly stunted by 28% (p=0.005) 20 days post-irradiation with GNPPEG-RGDcompared to control. No loss in overall survival or changes in bodyweight were measured post-injection of the GNP complexes.
Conclusion
We systematically determined the efficacy of clinically plausible GNPs as radiosensitizing agents for HDR-BT both in vitro and in vivo. Our results indicate that GNPs are safe and effective radiosensitizing agents for HDR-BT and demand further investigation into the safety and toxicity profiles for clinical trials.