Gold nanoparticles in ionizing radiation therapy of brain cancer

5750 Each year about 19,000 people in the United States are diagnosed with primary brain tumors. Overall, only about 30% of these cases are alive a year later. Although it is the most effective therapy for brain malignancy, ionizing radiation (IR) remains palliative because of radioresistance. The effect of ionizing radiation is achieved primarily through DNA damage in the irradiated cells. Sensitizing tumor cells to IR would result in a more effective radiation therapy. Gold nanoparticles (AuNP) are widely used in biological and biomedical applications. In a previous study a 200% enhancement of damage to a 5.6 Kbp DNA molecule conjugated to only ten 3nm AuNP was achieved after X-ray exposure. The combination of localized X-ray absorption, effective release of low-energy electrons, and efficient deposition of energy is the mechanism by which AuNP causes DNA damage. Therefore, we aimed to test the use of AuNP in a cellular system and assess its effect on DNA damage and cell killing after exposure to ionizing radiation. Cells from a medulloblastoma-derived cell line (Daoy) were incubated with positively-charged AuNP (TMA) or negatively-charged AuNP (MUA) for 24 hours, washed and then subjected to 0, 2, 4, 6, and 8 Gy of IR. Three days after irradiation, cellular growth was measured by MTT assay. At all IR doses about 50% cellular growth inhibition was observed in cultures treated with AuNP prior to irradiation compared to the growth of their irradiated-only counterparts. In another set of experiments, survival rate was evaluated 10 days after irradiation using the clonogenic assay. The survival rate of the AuNP-pretreated cultures was also about 50% lower than that of their irradiated-only counterparts. In addition, the AuNP effect was a dose and cell density dependent. A concentration of 1ug AuNP was sufficient to sensitize cells to IR when thinly seeded (500 cells per well) whereas in a 1000-cells per well density, a concentration of 10ug was required to sensitize the cells. To overcome cytotoxicity and improve cellular uptake, other types of AuNP coating-ligands are being explored ( e.g. , neutral and sugar ligands). In summary, these preliminary findings show the potential use of gold nanoparticles in radiation therapy of brain tumors.