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The safe, targeted and effective delivery of siRNA 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. The mean hydrodynamic size of these nanoparticles was systematically varied and optimized for delivery (40−100 nm). The magnetite nanoparticles delivery platform developed here offers the potential for magnetically guided targeting to the liver, as well as an opportunity to combine gene therapy with MRI imaging.