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. 2013 Mar 13;13(3):1059-64.
doi: 10.1021/nl304287a. Epub 2013 Feb 14.

Lipidoid-coated iron oxide nanoparticles for efficient DNA and siRNA delivery

Shan Jiang  1 , Ahmed A Eltoukhy, Kevin T Love, Robert Langer, Daniel G Anderson
Affiliations

Lipidoid-coated iron oxide nanoparticles for efficient DNA and siRNA delivery

Shan Jiang et al. Nano Lett. .

Abstract

The safe, targeted and effective delivery of gene therapeutics remains a significant barrier to their broad clinical application. Here we develop a magnetic nucleic acid delivery system composed of iron oxide nanoparticles and cationic lipid-like materials termed lipidoids. Coated nanoparticles are capable of delivering DNA and siRNA to cells in culture. The mean hydrodynamic size of these nanoparticles was systematically varied and optimized for delivery. While nanoparticles of different sizes showed similar siRNA delivery efficiency, nanoparticles of 50-100 nm displayed optimal DNA delivery activity. The application of an external magnetic field significantly enhanced the efficiency of nucleic acid delivery, with performance exceeding that of the commercially available lipid-based reagent, Lipofectamine 2000. The iron oxide nanoparticle delivery platform developed here offers the potential for magnetically guided targeting, as well as an opportunity to combine gene therapy with MRI imaging and magnetic hyperthermia.

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Figures

Figure 1
Figure 1
(a) schematic plot of the procedure of coating iron oxide nanoparticles; transmission electron microscopy (TEM) images of (b) particle clusters; (c) individual particles; (d) coating on the nanoparticle surface.
Figure 2
Figure 2
(a) Particle size measured by dynamic light scattering versus sonication time; (b) DNA delivery efficiency for nanoparticles of different sizes, (25 ng of DNA per well of a 96 well plate); (c) siRNA delivery efficiency for nanoparticles of different sizes (25 ng of siRNA per well of a 96 well plate).
Figure 3
Figure 3
Comparison of delivery efficiency with and without a magnet: (a) fluorescence microscopy images of cells after the transfection of plasmid DNA encoding green fluorescent protein (GFP) with and without the magnetic field; (b) fluorescence-activated cell sorting (FACS) analysis. Based on analysis of non-treated cells, cells to the right of the gate (blue line) were considered GFP-positive, while cells to the left of the gate were fluorescing at levels indistinguishable from background.
Figure 4
Figure 4
Comparison of the delivery efficiency with and without a magnetic field: (a) in vitro DNA delivery dose response, compared with Lipofectamine2000 at 25 ng DNA per well (0.05 nM); (b) DNA delivery efficiency upon varying the incubation time; (c) siRNA delivery dose response, relative toLipofectamine2000 at 25 ng siRNA per well (12.0 nM); (d) siRNA delivery efficiency upon varying the incubation time.
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