Magnetic Fe₃O₄ nanoparticles and chemotherapy agents interact synergistically to induce apoptosis in lymphoma cells

Int J Nanomedicine. 2010 Nov 19:5:999-1004. doi: 10.2147/IJN.S14957.

Abstract

The purpose of this study was to investigate the potential effects of combination therapy using magnetic nanoparticles of Fe₃O₄ (MNP-Fe₃O₄) and chemotherapeutic drugs on lymphoma cells. Proliferation, inhibition, and viability of Raji cells were detected by MTT and trypan blue exclusion. The percentage of cells undergoing apoptosis was detected by flow cytometry using fluorescein isothiocyanate-annexin V and propidium iodide staining. p53 and nuclear factor-κB (NF-κB) protein levels were measured by Western blot. The results showed that proliferation of Raji cells was inhibited by adriamycin or daunorubicin in a dose-and time-dependent manner. Cell sensitivity was improved and the 50% inhibitory concentrations of adriamycin and daunorubicin decreased when combined with a MNP-Fe₃O₄ carrier. Interestingly, increased apoptosis in Raji lymphoma cells was accompanied by upregulation of p53 protein and downregulation of NF-κB protein. Furthermore, the combination of MNP-Fe₃O₄ with adriamycin or daunorubicin increased p53 protein levels and decreased NF-κB protein levels more than adriamycin or daunorubicin alone, indicating that MNP-Fe₃O₄ could enhance the effect of chemotherapeutic drugs on p53 and NF-κB. Similar results for cell apoptosis and protein expression were not observed for the groups treated with dexamethasone ± MNP-Fe₃O₄ (P > 0.05). These findings suggest a potential clinical application for MNP-Fe₃O₄ in combination with daunorubicin or adriamycin in the treatment of lymphoma.

Keywords: NF-κB; Raji cells; apoptosis; magnetic nanoparticles; p53.

MeSH terms

  • Antibiotics, Antineoplastic / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Apoptosis / drug effects*
  • Blotting, Western
  • Burkitt Lymphoma / drug therapy*
  • Burkitt Lymphoma / metabolism
  • Burkitt Lymphoma / pathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Daunorubicin / pharmacology
  • Doxorubicin / pharmacology
  • Drug Synergism
  • Flow Cytometry
  • Humans
  • Magnetite Nanoparticles / chemistry*
  • NF-kappa B / metabolism
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Antibiotics, Antineoplastic
  • Magnetite Nanoparticles
  • NF-kappa B
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Doxorubicin
  • Daunorubicin