Optimising element choice for nanoparticle radiosensitisers

There is considerable interest in the use of heavy atom nanoparticles as theranostic contrast agents due to their high radiation cross-section compared to soft tissue. However, published studies have primarily focused on applications of gold nanoparticles. This study applies Monte Carlo radiation transport modelling using Geant4 to evaluate the macro- and micro-scale radiation dose enhancement following X-ray irradiation with both imaging and therapeutic energies on nanoparticles consisting of stable elements heavier than silicon. An approach based on the Local Effect Model was also used to assess potential biological impacts. While macroscopic dose enhancement is well predicted by simple absorption cross-sections, nanoscale dose deposition has a much more complex dependency on atomic number, with local maxima around germanium (Z = 32) and gadolinium (Z = 64), driven by variations in secondary Auger electron spectra, which translate into significant variations in biological effectiveness. These differences may provide a valuable tool for predicting and elucidating fundamental mechanisms of these agents as they move towards clinical application.

Gold nanoparticles as novel agents for cancer therapy

Gold nanoparticles are emerging as promising agents for cancer therapy and are being investigated as drug carriers, photothermal agents, contrast agents and radiosensitisers. This review introduces the field of nanotechnology with a focus on recent gold nanoparticle research which has led to early-phase clinical trials. In particular, the pre-clinical evidence for gold nanoparticles as sensitisers with ionising radiation in vitro and in vivo at kilovoltage and megavoltage energies is discussed.

Gold nanoparticle cellular uptake, toxicity and radiosensitisation in hypoxic conditions

Background and purpose: Gold nanoparticles (GNPs) are novel agents that have been shown to cause radiosensitisation in vitro and in vivo. Tumour hypoxia is associated with radiation resistance and reduced survival in cancer patients. The interaction of GNPs with cells in hypoxia is explored.

Materials and methods: GNP uptake, localization, toxicity and radiosensitisation were assessed in vitro under oxic and hypoxic conditions.

Results: GNP cellular uptake was significantly lower under hypoxic than oxic conditions. A significant reduction in cell proliferation in hypoxic MDA-MB-231 breast cancer cells exposed to GNPs was observed. In these cells significant radiosensitisation occurred in normoxia and moderate hypoxia. However, in near anoxia no significant sensitisation occurred.

Conclusions: GNP uptake occurred in hypoxic conditions, causing radiosensitisation in moderate, but not extreme hypoxia in a breast cancer cell line. These findings may be important for the development of GNPs for cancer therapy.