P 064 - Zero-valent Iron Nanoparticles Inhibited Head and Neck Cancer Cells Growth: A Pilot Evaluation and Mechanistic Characterization

Abstract

Nanomaterials were already identified to exhibit anti-cancer property without carrying drugs. We previously revealed the selective anti-cancer activity of Fe@Au nanoparticles (NP) by impairing mitochondria. The zero-valent iron (ZVI) core contributes the major cytotoxicity. Here, we screen oral cancer cells for resistance profile to ZVI NP and identify OECM1, OC3 and SCC9 to be sensitive, while HSC3, SAS and OC2 tolerate ZVI NP. Resistance clones of OECM1 also can be derived by pulsed NPs treatment. We identify that ZVI NP initiated Fenton reaction and induced free radicals with distinct difference in the mitochondria or cytosol between the refractory and sensitive cancer cells. Lipid peroxidation plays critical roles in the ZVI NP derived ROS induction and subsequent declined mitochondrial respiration. We further discovered the decrease of GPx upon ZVI treatment. GPx inhibitors and glutathione deprivation are able to sensitize ZVI refractory cancer cells accompanied by enhancing mitochondrial depolarization. These results reveal a potential anti-cancer mechanism of ZVI. We also demonstrate how to manipulate the ZVI resistance by combination therapy. This study provides biomarkers that predicts ZVI NP efficacy and new strategies to overcome ZVI resistance through integration of small molecular inhibitors in such new generational anti-cancer nanomedicine.