Enzyme and Cancer Cell Selectivity of Nanoparticles: Inhibition of 3-D Metastatic Phenotype and Experimental Melanoma by Zinc Oxide
Biomedical applications for metal and metal oxide nanoparticles are rapidly increasing. Here their functional impact on two well-characterized model enzymes, Luciferase (Luc) or β-galactosidase (β-Gal) was quantitatively compared. Nickel oxide nanoparticle (NiO-NP) activated β-Gal (>400% control) and boron carbide nanoparticle (B4C-NP) inhibited Luc (<10% control), whereas zinc oxide (ZnO-NP) and cobalt oxide (Co3O4-NP) activated β-Gal to a lesser extent and magnesium oxide (MgO) moderately inhibited both enzymes. Melanoma specific killing was in the order; ZnO > B4C = Cu > MgO > Co3O4 > Fe2O3 > NiO, ZnO-NP inhibiting B16F10 and A375 cells as well as ERK enzyme (>90%) and several other cancer-associated kinases (AKT, CREB, p70S6K). ZnO-NP or nanobelt (NB) serve as photoluminescence (PL) cell labels and inhibit 3-D multi-cellular tumor spheroid (MCTS) growth and were tested in a mouse melanoma model. These results demonstrate nanoparticle and enzyme specific biochemical activity and suggest their utility as new tools to explore the important model metastatic foci 3-D environment and their chemotherapeutic potential.
Luciferase (Luc), Metal Oxide Nanoparticle (MONP), Multi-Cellular Tumor Spheroids (MCTS), Nano-Belt (NB), Photoluminescence (PL), Two Dimensional Fluorescence Difference Spectroscopy (2-D FDS), β-Galactosidase (β-Gal)
DeLong, Robert K., Jennifer A. Mitchell, R. Tyler Morris, Jeffrey Comer, Miranda N. Hurst, Kartik Ghosh, Adam Wanekaya et al. "Enzyme and cancer cell selectivity of nanoparticles: inhibition of 3-D metastatic phenotype and experimental melanoma by zinc oxide." Journal of biomedical nanotechnology 13, no. 2 (2017): 221-231.
Journal of Biomedical Nanotechnology