This work presents an in-depth analysis into the dependencies of radiosensitisation on X-ray beam energy, particle morphology and particle concentration for Ta2O5 nanostructured particles. A maximum sensitisation enhancement ratio of 1.46 was attained with irradiation of a 10 MV X-ray photon beam on 9L cells exposed to the less aggregated form of nanostructured particles at 500 μg/mL. A significant increase in sensitisation of 30% was noted at 150 kVp for irradiation of the less aggregated form of tantalum pentoxide nanostructured particles compared to its more agglomerated counterpart. Interestingly, no differences in sensitisation were observed between 50 and 500 μg/mL for all beam energies and nanostructured particles tested. This is explained by a physical "shell effect", where by the nanostructured particles form layers around the cells (observed using confocal microscopy), with the inner layers contributing to enhancement, while the outer layers shield the cell from damage.