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

J Biomed Nanotechnol. 2017 Feb;13(2):221-31. doi: 10.1166/jbn.2017.2336.

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.

Keywords: Metal Oxide nanoparticle (MONP); β-Galactosidase (β-Gal); Luciferase (Luc); Two Dimensional Fluorescence Difference Spectroscopy (2D FDS); Photoluminescence (PL0; Multi-Cellular Tumor Spheroids (MCTS); Nano-Belt (NB).

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Luciferases / analysis
  • Luciferases / drug effects
  • Luciferases / metabolism
  • Melanoma, Experimental / metabolism*
  • Metal Nanoparticles / chemistry*
  • Metals, Heavy / pharmacology
  • Mice
  • Spheroids, Cellular / drug effects*
  • Zinc Oxide / chemistry
  • Zinc Oxide / pharmacology*
  • beta-Galactosidase / analysis
  • beta-Galactosidase / drug effects
  • beta-Galactosidase / metabolism

Substances

  • Antineoplastic Agents
  • Metals, Heavy
  • Luciferases
  • beta-Galactosidase
  • Zinc Oxide