PHRM-02. DELIVERY OF CHEMOTHERAPEUTICS TO PEDIATRIC BRAIN TUMORS USING CITRATE-CAPPED GOLD NANOPARTICLES

Abstract

Medulloblastomas and gliomas account for nearly 28% of primary tumors and about 80% of malignant tumors in children. Many of the chemo-drugs that are found effective in killing tumor cells perform well in laboratory settings but fail to cross the blood-brain barrier in humans in direct clinical applications. This problem is overcome by using carriers which could deliver the drugs across the blood-brain barrier. To increase the efficacy of drugs in targeting different tumors, different nanoparticles have been used as carriers in the recent past. Some drugs, including AZD-1775 and Gemcitabine, have been shown by researchers to be effective in multiple brain tumors but have not been adequately utilized alone and/or in combination in pediatric brain tumor patients. In our study, we have conjugated AZD-1775 and Gemcitabine to citrate-capped gold nanoparticles (AuNPs). Cells have been treated with a drug alone, or AuNP alone and AuNP conjugated with drugs for 72 hours. Cell viability assays, cell cycle analysis and western blotting have been used to evaluate the delivery of drug to cells. Both the drugs and their AuNP-conjugates inhibited the growth of cells tested. AuNPs conjugated with the drugs showed more effective delivery of the drugs to cells than drugs alone at the same concentrations, as measured by tumor cell growth. Also, our initial in vivo study shows prolonged survival of mice bearing brain tumors treated with AuNP-conjugated AZD-1775 than those treated with AZD-1775 alone. These results confirm that AuNPs are a suitable platform to deliver chemotherapeutics to brain tumors.