Gareth Wakefield, Martin Gardener, Matt Stock and Megan Adair
Titanium oxide is a photoactive material that generates hydroxyl free radicals via water splitting. When doped with rare earth ions titanium oxide nanoparticles are activated by X-rays and X-ray generated electrons and are used to enhance radiotherapy treatment of solid tumours. As the nanoparticles generate free radicals by water splitting the presence of molecular oxygen is not required and aggressive hypoxic tumours may be targeted. A clonogenic assay of radio resistant pancreatic cancer (PANC- 1) cells shows a radiotherapy dose enhancement factor of 1.9 at clinically relevant nanoparticle loadings. A fast growing oropharyngeal cancer (FaDu) xenograft demonstrates that rare earth doped titanium oxide nanoparticles delivered by intratumoural injection disperse throughout the tumour, being taken up by cancer cells and undergoing passive accumulation in the Golgi apparatus. Incident radiotherapy activates the nanoparticles to produce hydroxyl free radicals, destroying the Golgi apparatus, and inducing tumour cell apoptosis. This results in a reduction in proliferating cancer cells and a consequent reduction in tumour regrowth rate by a factor of 3.8. There is no increase in systemic toxicity when using nanoparticles in addition to radiotherapy. Rare earth doped titanium oxide nanoparticles therefore represent a novel approach to tumour treatment via destruction of the cells Golgi apparatus during radiotherapy.
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