Very high energy electron radiotherapy and gold nanoparticle radiosensitisation: Quantifying DNA damage enhancement in pBR322 plasmids.

While novel radiotherapy modalities such as VHEE (Very High Energy Electron) and FLASH are being developed as effective potential cancer treatments, exposure of healthy cells to dose during radiotherapy remains a major challenge. Use of high-Z nanoparticles, in particular gold nanoparticles (AuNPs) has been identified as a method of radiosensitisation - increasing the toxicity of ionising radiation in a localised tumour region while avoiding dose increase to healthy tissue. This study focuses on AuNP radiosensitisation in VHEE irradiation with an investigation into dose enhancement through physical mechanisms. pBR322 plasmid DNA in solution with AuNPs was irradiated with VHEE beams at the CLEAR facility (CERN), with resulting lethal double-strand break (DSB) yields measured. AuNP size and beam energy were varied, in addition to dose rate to determine if a FLASH effect on DSB yield was observed. Significant increases in DSB yield were observed for samples containing 10 nm or 40 nm AuNPs, with dose enhancement factors of 1.21-1.34 and 1.27-1.50 for 10 and 40 nm AuNPs respectively. Such dose enhancement was found to be independent of electron beam energy across the range of 106-201 MeV. No significant variation in dose enhancement factor was observed between low and ultra-high dose rate irradiation. This study, having indicated significant increases in physical radiation effects through inclusion of AuNPs, highlights the potential for incorporating AuNPs in VHEE radiotherapy to increase the subsequent biological effects and improve clinical outcomes in addition to its potential to improve image contrasting.