Chitosan-coated superparamagnetic iron oxide nanoparticles for doxorubicin delivery: synthesis and anticancer effect against human ovarian cancer cells

Chem Biol Drug Des. 2013 Sep;82(3):296-306. doi: 10.1111/cbdd.12145. Epub 2013 Jul 25.

Abstract

Doxorubicin-loaded chitosan-coated superparamagnetic iron oxide nanoparticles (Fe3 O4 ; SPIO-NPs) were prepared by coprecipitation and emulsification cross-linking method and uniform NPs with an average particle size of 82 nm, with high encapsulation efficiencies, were obtained. The drug-loading efficiency of doxorubicin (3.2 mg/mg NPs) showed better results for the chitosan-loaded SPIO-NPs as compared to the bare ones (0.5 mg/mg; p < 0.05). The incubation of A2780 and OVCAR-3 human ovarian cancer cells with doxorubicin-loaded and doxorubicin-loaded chitosan-coated SPIO-NPs, for 24, 48, 72, 96, and 120 h, showed significant IC50 (2.0 ± 0.6 and 7.1 ± 2.7 mm doxorubicin) and IC90 (4.0 ± 9.2 and 10 ± 0.5 mm doxorubicin), respectively, after 96 h of incubation. While, 95% and 98% growth inhibition was seen in A2780 and OVCAR-3 cells after the 96-h exposure to the doxorubicin-chitosan-SPIO-NPs (p < 0.05). A 5-day (120 h) incubation with doxorubicin-chitosan-SPIO-NPs showed that A2780 and OVCAR-3 cells were able to uptake 120 and 110 pg iron/cell, respectively, when treated with doxorubicin-chitosan-SPIO-NPs for 72 h (p < 0.05).

Keywords: chitosan; doxorubicin; drug loading; encapsulation; human ovarian cancer; iron oxide.

MeSH terms

  • Antibiotics, Antineoplastic / chemistry*
  • Antibiotics, Antineoplastic / toxicity
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Chitosan / chemistry*
  • Doxorubicin / chemistry*
  • Doxorubicin / toxicity
  • Drug Carriers / chemistry*
  • Female
  • Ferric Compounds / chemistry*
  • Humans
  • Hydrogen-Ion Concentration
  • Inhibitor of Apoptosis Proteins / metabolism
  • Magnetite Nanoparticles / chemistry*
  • Magnetite Nanoparticles / ultrastructure
  • NF-kappa B / metabolism
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Particle Size
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Survivin
  • bcl-2-Associated X Protein / metabolism

Substances

  • Antibiotics, Antineoplastic
  • BIRC5 protein, human
  • Drug Carriers
  • Ferric Compounds
  • Inhibitor of Apoptosis Proteins
  • Magnetite Nanoparticles
  • NF-kappa B
  • Proto-Oncogene Proteins c-bcl-2
  • Survivin
  • bcl-2-Associated X Protein
  • ferric oxide
  • Doxorubicin
  • Chitosan