Therapeutic enhancement effects using a lower energy 2.5 MV photon beam combined with gold nanoparticles on the BxPC-3 pancreatic cancer cell line,in vitro.

Abstract

Objective. This study investigates the feasibility of using a clinically relevant lower energy 2.5 megavoltage (MV) photon beam in combination with gold nanoparticles (GNPs).Approach.Pancreatic cancer cell line, BxPC-3 impregnated with GNPs were exposedin vitroto 2.5 MV photon beam and compared with orthovoltage 225 kV and clinical 6 MV photon beam. Bare, 50 nm diameter, spherical GNPs were introduced in the cell culture 24 h prior to irradiation at a concentration of either 10μg ml^-1or 50μg ml^-1. GNP uptake was determined using inductively coupled plasma optical emission spectroscopy. The cells were irradiated with doses between 0 Gy to 8 Gy. Cell survival curves were obtained via clonogenic assay using immediate or delayed plating (24 h) methods 12 d after irradiation. The terminal deoxynucleotidyl transferase dUTP nick end labeling assay was used to evaluate DNA damage at two time points post irradiation, immediate and 24 h for 1 Gy and 6 Gy.Main results. The enhancement factor (EF) in BxPC-3 cells was greatest for cells incubated with 50μg ml^-1of GNPs analyzed immediately post irradiation. Cells irradiated with 225 kV showed greatest EF (1.57 ± 0.15), followed by 2.5 MV (1.51 ± 0.04). The lowest EF was seen for 6 MV, immediate plating (1.10 ± 0.04). A significant increase in the number of DNA double strand breaks (DSB) was observed in cells incubated with 50μg ml^-1of GNPs irradiated at 6 Gy with 225 kV and 2.5 MV. There was no significant increase in DSBs for the cells irradiated with 6 MV.Significance.These results suggest that the 2.5 MV could be a compromise between an orthovoltage energy beam and a clinical 6 MV beam, showing comparable reduction in cell survival to the 225 kV beam. Future GNP radiation enhancement research may focus on intermediate energy beams.