Nanoceria-mediated delivery of doxorubicin enhances the anti-tumour efficiency in ovarian cancer cells via apoptosis

Sci Rep. 2017 Aug 25;7(1):9513. doi: 10.1038/s41598-017-09876-w.

Abstract

Nanocarriers are widely used for effective delivery of anticancer drugs to tumours with potential to improve cancer treatment. Here, we developed a nanoceria (CeO2)-based system for delivery of the anti-cancer drug doxorubicin (DOX) to human ovarian cancer cells. Negatively charged nanoceria could conjugate with the cationic DOX via electrostatic interaction under physiological conditions, forming DOX-loaded nanoceria (CeO2/DOX). CeO2/DOX particles displayed nearly spherical shapes, along with superior drug-loading content (22.41%), loading efficiency (99.51%), and higher cellular uptake and drug release behaviours compared to free DOX. Moreover, DOX was released faster from CeO2/DOX under reductive acidic conditions (pH 5.0, 10 mM glutathione) than under physiological conditions (pH 7.4). The initial intracellular DOX concentration was higher in the free DOX groups than in the CeO2/DOX groups, but quickly reduced to 25% of the initial concentration after 24-h culture. By contrast, CeO2/DOX showed sustained DOX release over time and maintained a high intracellular DOX concentration for up to 72 h. In vitro assays showed that CeO2/DOX exhibited higher cell proliferation inhibition and apoptosis compared with free DOX. These results highlight DOX-loaded nanoceria as a promising therapeutic agent for cancer treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Cerium / chemistry
  • Doxorubicin / administration & dosage*
  • Drug Carriers* / chemistry
  • Drug Liberation
  • Female
  • Humans
  • Nanoparticles* / chemistry
  • Nanoparticles* / ultrastructure
  • Ovarian Neoplasms

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Cerium
  • ceric oxide
  • Doxorubicin