Cytotoxic effects and apoptosis induction of cisplatin-loaded iron oxide nanoparticles modified with chitosan in human breast cancer cells

Mol Biol Rep. 2019 Oct;46(5):5033-5039. doi: 10.1007/s11033-019-04954-w. Epub 2019 Jul 5.

Abstract

Cisplatin is widely used as an anticancer drug in chemotherapy of human cancers. In the field of cancer therapy, nanoparticles modified with biocompatible copolymers are suitable vehicles to effectively deliver smaller doses of hydrophobic drugs such as cisplatin in the body. In this study, we investigated whether cisplatin-loaded iron oxide nanoparticles (IONPs) modified with chitosan can exert cytotoxic effects in the human breast cancer cell line MDA-MB-231. IONPs was synthesized using eucalyptus leaf extract as a reducing and stabilizing agent. MDA-MB-231 cells were treated with different concentrations of cisplatin, cisplatin-IONPs and cisplatin-IONPs-chitosan for 24 h. Apoptosis was confirmed by flow cytometry, whereas The mRNA and protein expression of pro- and anti-apoptotic molecules were measured using Real time RT-PCR and western blotting. Treatment with both cisplatin-IONPs and cisplatin-IONPs-chitosan showed a significantly higher cytotoxic effect in comparison to the free drug alone in MDA-MB-231 cells. The levels of apoptosis in cells treated with a combination of cisplatin-IONPs-chitosan were significantly higher compared with cisplatin-IONPs and cisplatin alone. The results of this study showed that the interaction between cisplatin and iron oxide nanoparticles modified with chitosan could enhance responsiveness to cisplatin in breast cancer cells.

Keywords: Apoptosis; Cell viability; Cisplatin; Cytotoxicity; Iron oxide nanoparticle.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Cell Death / drug effects
  • Cell Line, Tumor / drug effects
  • Chitosan / therapeutic use
  • Cisplatin / metabolism
  • Cisplatin / pharmacology*
  • Drug Delivery Systems / methods
  • Female
  • Ferric Compounds / therapeutic use
  • Humans
  • Metal Nanoparticles / therapeutic use*
  • Nanoparticles / chemistry

Substances

  • Antineoplastic Agents
  • Ferric Compounds
  • ferric oxide
  • Chitosan
  • Cisplatin