Serum adsorption, cellular internalization and consequent impact of cuprous oxide nanoparticles on uveal melanoma cells: implications for cancer therapy

Nanomedicine (Lond). 2015;10(24):3547-62. doi: 10.2217/nnm.15.178. Epub 2015 Oct 15.

Abstract

Aim: To investigate the biological fate of cuprous oxide nanoparticles (Cu2O-NPs) and to evaluate their potential in uveal melanoma therapy.

Materials & methods: The protein corona, cellular uptake mechanism and localization of Cu2O-NPs were investigated. Furthermore, the effect of Cu2O-NPs on uveal melanoma cell proliferation, migration and invasion, and possible mechanisms were studied in detail.

Results: Cu2O-NPs are able to adsorb serum proteins in cell culture medium, which are then internalized by uveal melanoma cells mainly through lipid raft-mediated endocytosis. Furthermore, Cu2O-NPs selectively inhibit cancer cell growth and impair the ability of uveal melanoma cell migration, invasion and the cytoskeleton assembly. The mechanism may be that Cu2O-NPs located in and damage mitochondria, autophagolysosomes and lysosomes, leading to elevated reactive oxygen species level and over-stimulated apoptosis and autophagy.

Conclusion: The data provide detailed information of Cu2O-NPs for further application and indicate that Cu2O-NPs could be a potential agent for uveal melanoma therapy.

Keywords: cellular uptake; cuprous oxide nanoparticles; programmed cell death; protein corona; uveal melanoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Copper / administration & dosage
  • Copper / chemistry*
  • Humans
  • Melanoma / drug therapy*
  • Melanoma / pathology
  • Nanoparticles / administration & dosage
  • Nanoparticles / chemistry*
  • Neoplasm Invasiveness / pathology
  • Uveal Neoplasms / drug therapy*
  • Uveal Neoplasms / pathology

Substances

  • Copper
  • cuprous oxide

Supplementary concepts

  • Uveal melanoma