Zinc Oxide Nanoparticle-Poly I:C RNA Complexes: Implication as Therapeutics against Experimental Melanoma

Mol Pharm. 2017 Mar 6;14(3):614-625. doi: 10.1021/acs.molpharmaceut.6b00795. Epub 2017 Feb 14.

Abstract

There is current interest in harnessing the combined anticancer and immunological effect of nanoparticles (NPs) and RNA. Here, we evaluate the bioactivity of poly I:C (pIC) RNA, bound to anticancer zinc oxide NP (ZnO-NP) against melanoma. Direct RNA association to unfunctionalized ZnO-NP is shown by observing change in size, zeta potential, and absorption/fluorescence spectra upon complexation. RNA corona was visualized by transmission electron microscopy (TEM) for the first time. Binding constant (Kb = 1.6-2.8 g-1 L) was determined by modified Stern-Volmer, absorption, and biological surface activity index analysis. The pIC-ZnO-NP complex increased cell death for both human (A375) and mouse (B16F10) cell lines and suppressed tumor cell growth in BALB/C-B16F10 mouse melanoma model. Ex vivo tumor analysis indicated significant molecular activity such as changes in the level of phosphoproteins JNK, Akt, and inflammation markers IL-6 and IFN-γ. High throughput proteomics analysis revealed zinc oxide and poly I:C-specific and combinational patterns that suggested possible utility as an anticancer and immunotherapeutic strategy against melanoma.

Keywords: antimelanoma; binding parameters; immunology; poly I:C RNA (pIC); zinc oxide nanoparticles (ZnO-NPs).

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Biomarkers, Tumor / metabolism
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-6 / metabolism
  • MAP Kinase Kinase 4 / metabolism
  • Melanoma, Experimental / drug therapy*
  • Melanoma, Experimental / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles / administration & dosage*
  • Poly I-C / pharmacology*
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA / pharmacology*
  • Zinc Oxide / pharmacology*

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Interleukin-6
  • RNA
  • Interferon-gamma
  • Proto-Oncogene Proteins c-akt
  • MAP Kinase Kinase 4
  • Poly I-C
  • Zinc Oxide