Enhanced transfection rates of small-interfering RNA using dioleylglutamide-based magnetic lipoplexes

Nucleic Acid Ther. 2011 Jun;21(3):165-72. doi: 10.1089/nat.2010.0274.

Abstract

Magnetic force-guided delivery (magnetofection) has been studied as a new modality for introducing small-interfering RNA (siRNA) into target cells, but its delivery efficiency needs to be improved. Here, we report that magnetofection of N,N''-dioleylglutamide (DG)-based magnetic lipoplexes can substantially enhance the cellular delivery rates of siRNA. The siRNA was triply complexed with DG-based cationic liposomes and cationic iron-oxide nanoparticles. The formation of siRNA-containing magnetic lipoplexes was confirmed by gel retardation, sizes, and zeta potential values. Fluorescence microscopy and flow cytometry of fluorescent marker-labeled siRNA revealed that the DG-based magnetic lipoplexes conferred a higher cellular delivery rate of siRNA than DG-based lipoplexes or Lipofectamine 2000. In addition to the enhanced delivery of siRNA, the DG-based magnetic lipoplexes showed lack of cytotoxicity. We then tested the application of these magnetic lipoplexes for the cellular delivery of anticancer siRNA. Cancer cell lines magnetofected with DG-based magnetic lipoplexes containing Mcl1-specific siRNA (siMcl1) showed much lower viability than the groups treated with DG-based lipoplexes or Lipofectamine 2000, indicating that our magnetofection strategy conferred greater siMcl1-induced anticancer activity. These results suggest that DG-based magnetic lipoplexes are promising candidates for enhancing the efficiency of magnetic field-guided siRNA delivery.

MeSH terms

  • Cell Line, Tumor
  • Cell Survival
  • Glutamine / analogs & derivatives*
  • Glutamine / chemistry
  • HeLa Cells
  • Humans
  • Lipopeptides / chemistry*
  • Liposomes
  • Magnetite Nanoparticles / administration & dosage*
  • Magnetite Nanoparticles / chemistry
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • RNA, Small Interfering / administration & dosage*
  • RNA, Small Interfering / chemistry
  • Transfection / methods*

Substances

  • Lipopeptides
  • Liposomes
  • Magnetite Nanoparticles
  • Myeloid Cell Leukemia Sequence 1 Protein
  • N,N'-dioleylglutamide
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Small Interfering
  • Glutamine