Objectives: This study aims to investigate the property of an iron core-gold-shell superparamagnetic nanoparticle (Fe@Au)for its potential applications in oral cancer therapy. Methods: The Fe@Au nanoparticles were synthesized by modify a reverse micelle method and was analyzed by TEM and ESCA for its physical property and surface chemistry. WST-1 and BrdU assays were performed and compared between cultured normal oral keratinocytes and four oral cancer cell lines. The combined selective cytotoxic effect of Fe@Au with free or covalently attached methotrexate (MTX) was compared. Results: The Fe@Au showed a monodispersive size of 22nm and a complete surface coverage of a gold shell. WST-1 assay presented a selective cytotoxic effect of the nanoparticles to the cancer cell lines but not normal oral keratinocytes and a synergistic effect was observed when combined with free methotrexate. Inhibition of DNA synthesis in the cancer cells presented a dose dependent profile in a parallel association with the WST-1 results. A potential mechanism of selectivity through mitochondria pathway was demonstrated by FACS analysis of a mitochondrial membrane potential dye. Conclusions: the Fe@Au superparamagnetic nanoparticles demonstrated a selective cytotoxic effect to oral cancer cells. Combined its superparamegnetic property and synergistic effect with anti-cancer drugs, the core-shell nanoparticle may be further engineered for a new class of anti-cancer agent with magnetic guiding feature, potential MRI diagnostic contrast and cancer selective therapeutic effect.

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