Nanoparticle-based delivery of an anti-proliferative metal chelator to tumor cells

This paper describes the preparation and characterization of polymeric nanoparticles loaded with a potent anti-tumor metal chelator, Di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT) for delivery to cancer cells. Metal chelators have been increasingly studied for their anti-cancer properties that rely on the high demand of neoplastic cells for iron. Dp44mT has previously shown great antiproliferative characteristics in several cancers including breast cancer and melanoma. To further expand the application of this highly cytotoxic agent for cancer treatment and to enable its specific delivery to malignant cells, here we apply nano-scale particles (NPs) of biodegradable poly(lactic-co-glycolide) (PLGA) for encapsulation of Dp44mT and evaluate its effectiveness in vitro. The results demonstrated that Dp44mT was efficiently encapsulated in PLGA particles. Resulting NPs were uniform in size and shape and had good colloidal stability. Moreover, Dp44mT encapsulation in PLGA enhanced the water solubility of this agent. Lastly, the present formulation showed high level of cytotoxicity in glioma cells. Together, these results show the potential of PLGA NPs as a nano-carrier for Dp44mT with no apparent impact on the anti-tumor activity of this compound.