Nanostructures, concentrations and energies: an ideal equation to extend therapeutic efficiency on radioresistant 9L tumor cells using ceramic nanostructured particles

Ryan Brown,Konstantin Konstantinov,Stéphanie Corde,Moeava Tehei,Sianne Oktaria,Michael Lerch,Anatoly Rosenfeld

doi:10.1088/2057-1976/aa56f2

Abstract

This work presents an in-depth analysis into the dependencies of radiosensitisation on x-ray beam energy, particle morphology and particle concentration for nanostructured particles (NSPs). 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 NSPs at 500 μg ml−1. A significant increase in sensitisation of 30% was noted at 150 kVp for irradiation of the less aggregated form of tantalum pentoxide NSPs compared to its more agglomerated counterpart. Interestingly, no differences in sensitisation were observed between 50 and 500 μg ml−1 for all beam energies and NSPs tested. This is explained by a physical ‘shell effect’, where by the NSPs 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.

Highlights

Nanostructures, concentrations and energies: an ideal equation to extend therapeutic efficiency on radioresistant 9L tumor cells using
Characterisation of nanostructured particles (NSPs) crystal structure Diffraction patterns were constructed for each NSP, shown in figure 1, with each curve containing peaks of similar shape, intensity and position, indicative that the NSP samples are of similar atomic composition, namely Ta2O5
Peak analysis and database comparison of the diffraction patterns revealed the thermal nanostructured particles (TNSPs) to be orthorhombic beta phase (JCPDS:250922), while the precipitation nanostructured particles (PNSPs) are hexagonal delta phase (JCPDS:19-1299). This structural difference is fundamentally linked to the production methods employed for each NSP, where by the annealing temperature of 700 °C produces hexagonal phase Ta2O5 for the PNSPs, as opposed to 800 °C for the TNSPs, which results in orthorhombic formation

Summary

Introduction

Nanostructures, concentrations and energies: an ideal equation to extend therapeutic efficiency on radioresistant 9L tumor cells using. Cancerous disease accounts for 1 in 8 deaths worldwide [1] with over 50% of patients [2] utilising some form of radiotherapy in their treatment plan This method relies on x-rays irradiating the target volume, it is difficult to maximise damage to the tumor volume, increasing tumor control probability, while sparing healthy tissue. Known as dose enhancement radiotherapy (DERT), this technique involves the introduction of high-Z atoms into close proximity to the tumor which, following exposure from the local radiation field, increases the selective damage and killing of the tumor cells. This radiation-induced increase in radiosensitivity is facilitated by the production of charged particles and reactive oxygen species (ROS), which are created when incoming photons interact with target high-Z atoms.

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