Enzyme and Cancer Cell Selectivity of Nanoparticles: Inhibition of 3-D Metastatic Phenotype and Experimental Melanoma by Zinc Oxide

Robert K. DeLong, Jennifer A. Mitchell, R. Tyler Morris, Jeffrey Comer, Miranda N. Hurst, Kartik Ghosh, Adam Wanekaya, Miranda Mudge, Ashley Schaeffer, Laurie L. Washington, Azure Risor-Marhanka, Spencer Thomas, Shanna Marroquin, Amber Lekey, Joshua J. Smith, Richard Garrad, Santosh Aryal, Mohamed Abdelhakiem, Garry P. Glaspell

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)221-231
Number of pages11
JournalJournal of Biomedical Nanotechnology
Volume13
Issue number2
DOIs
StatePublished - Feb 2017

Keywords

  • 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)

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