Selective cancer cell toxicity and radiosensitization using different high atomic number nanoparticles

Grellet, S.; Kaas, S.; Crabb, E.; Allman, S. and Golding, J. (2016). Selective cancer cell toxicity and radiosensitization using different high atomic number nanoparticles. In: Nanotech France 2016, 1-3 Jun 2016, Paris, France.

Abstract

Radiotherapy is currently used in around 50% of cancer treatments. Although it is generally effective, it is damaging to surrounding healthy tissues. This damage can be reduced by by better targeting to cancer cells. Improved radiotherapy outcomes can be achieved by targeting heavy elements to cancer cells, since these produce energetic electrons and free radicals upon irradiation that further increase the effectiveness of radiotherapy. Because of their biocompatibility and amenability to surface modification, gold nanoparticles (AuNPs) show significant promise in this area.We observe that acute 3hr exposure of cells to 2nm gold nanoparticles, bearing a 50:50 ratio of alpha-galactose and PEGamine ligands, results in selective chemotoxicity toward cancer cells at nanomolar concentrations, without affecting normal cells (Figure 1). Chemotoxicity is prevented by antioxidant co-administration and is partially prevented by a pan-caspase inhibitor (ZVAD- fmk). Our initial results suggest that AuNP toxicity is additive with using X-ray radiotherapy. Cerium oxide NPs are one of the most studied metal oxides NPs due to their high redox and oxygen transport properties [1]. They are interesting for radiotherapy applications because they adsorb oxygen and may therefore favour the radiolytic production of oxygen-containing free radicals, especially under low-oxygen conditions, such as the environment of most solid tumours. The surface oxygen vacancy of ceria NPs therefore makes them an interesting tool for prooxidant properties [2,3]. Nevertheless, the potential of ceria as a radiosensitiser has not been investigated extensively as it has a relatively low atomic number. It will therefore produce a low flux of secondary electrons upon irradiation which could potentially displace the adsorbed oxygen. We have been working on the fabrication of mixed ceria NPs, incorporating gold or bismuth, to increase the flux of secondary electrons (Figure 2). It is hoped these effects combined will further facilate the localized generation of ROS and increase effectiveness of targetted radiotherapy We predict that these new mixed-oxide ceria NPs will have better radiosensitisation potential than pure ceria NPs, and could be used to effectively target hypoxic cancer cells.

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