DESIGNING NANOCHELATORS FOR CANCER THERAPY
Abstract
Iron catalyzes cytosolic reactions that promote cancer cell proliferation. The latter is responsible for the poor survival rate of cancer patients. One approach to reduce iron enhanced tumor growth is through the use of iron chelators that are site-directed to the tumor site. This paper reports a simple method for designing gold nanoparticles (AuNPs) as a molecular vehicles to transport folic acid targeting moieties and 5-amino-8-hydroxyquinoline (AHQ) iron chelators to cancer cells. The AHQ chelators and folic acid targeting moieties were coupled to glutathione synthon for surface conjugation to AuNPs. Thin layer chromatography (TLC), and infrared (IR), and 1H-NMR spectroscopies determined the surface-modified AuNPs were pure with no excess ligands and provide evidence for conjugation of the chelator and targeting moiety to the AuNPs surface. Fluorescence spectroscopy also confirmed the presence of the ligands on the AuNP surface. The capacity of the gold nanochelators to bind to metals was assessed by UV-Vis and dynamic light scattering (DLS) spectroscopies upon incubation with different types of metal ion and at different concentrations. We can preliminary rank the metal binding affinities to the nanochelators in order of decreasing affinity as follows: Cu(II) > Zn(II) > Fe(III) > Ca(II) > K(I) > Na(I) at pH 6.5 and K(I) > Cu(II) > Na(I) > Zn(II) > Ca(II) > Fe(III) at pH 8.0. The synthetic route employed allows for the development of a library of tailored and targeted chelator ligands using biocompatible AuNPs with high potential towards controlling iron concentrations in cancer cells.