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.
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