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Abstract
Radiotherapy (RT) is an effective cancer treatment modality, but standard RT often causes collateral damage to nearby healthy tissues. To increase therapeutic ratio, radiosensitization via gold nanoparticles (GNPs) has been shown to be effective. One challenge is that megavoltage beams generated by clinical linear accelerators are poor initiators of the photoelectric effect. Previous computer models predicted that a diamond target beam (DTB) will yield 400% more low-energy photons, increasing the probability of interacting with GNPs to enhance the radiation dose by 7.7-fold in the GNP vicinity. After testing DTB radiation coupled with GNPs in multiple cell types, we demonstrate decreased head-and-neck cancer (HNC) cell viability in vitro and enhanced cell-killing in zebrafish xenografts compared to standard RT. HNC cell lines also displayed increased double-stranded DNA breaks with DTB irradiation in the presence of GNPs. This study presents preclinical responses to GNP-enhanced radiotherapy with the novel DTB, providing the first functional data to support the theoretical evidence for radiosensitization via GNPs in this context, and highlighting the potential of this approach to optimize the efficacy of RT in anatomically difficult-to-treat tumors.
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1 Dalhousie University, Department of Biology, Halifax, Canada (GRID:grid.55602.34) (ISNI:0000 0004 1936 8200); IWK Health Centre/Dalhousie University, Department of Pediatrics, Halifax, Canada (GRID:grid.55602.34) (ISNI:0000 0004 1936 8200)
2 Dalhousie University, Department of Physics and Atmospheric Science, Halifax, Canada (GRID:grid.55602.34) (ISNI:0000 0004 1936 8200)
3 University of Ottawa, Children’s Hospital of Eastern Ontario Research Institute/Department of Pediatrics, Ottawa, Canada (GRID:grid.28046.38) (ISNI:0000 0001 2182 2255)
4 IWK Health Centre/Dalhousie University, Department of Pediatrics, Halifax, Canada (GRID:grid.55602.34) (ISNI:0000 0004 1936 8200)
5 IWK Health Centre/Dalhousie University, Department of Pediatrics, Halifax, Canada (GRID:grid.55602.34) (ISNI:0000 0004 1936 8200); University of Ottawa, Children’s Hospital of Eastern Ontario Research Institute/Department of Pediatrics, Ottawa, Canada (GRID:grid.28046.38) (ISNI:0000 0001 2182 2255)
6 Dalhousie University, Department of Physics and Atmospheric Science, Halifax, Canada (GRID:grid.55602.34) (ISNI:0000 0004 1936 8200); Dalhousie University, Department of Radiation Oncology, Halifax, Canada (GRID:grid.55602.34) (ISNI:0000 0004 1936 8200)
7 Dalhousie University, Department of Radiation Oncology, Halifax, Canada (GRID:grid.55602.34) (ISNI:0000 0004 1936 8200)