title: Lipidoid-coated iron oxide nanoparticles for efficient DNA and siRNA delivery.
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.
authors: Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
authors: Shan
authors: S
authors: Jiang
authors: Ahmed A
authors: AA
authors: Eltoukhy
authors: Kevin T
authors: KT
authors: Love
authors: Robert
authors: R
authors: Langer
authors: Daniel G
authors: DG
authors: Anderson
mesh_terms: D004247:DNA / Q000008:administration & dosage*; D005290:Ferric Compounds / Q000008:administration & dosage*; D008055:Lipids / Q000737:chemistry*; D053768:Metal Nanoparticles; D046529:Microscopy, Electron, Transmission; D034741:RNA, Small Interfering / Q000008:administration & dosage*
chemical_list: D005290:Ferric Compounds; D008055:Lipids; D034741:RNA, Small Interfering; C000499:ferric oxide; D004247:DNA
references: Acc Chem Res. 2011 Oct 18;44(10):842-52
references: 21661727
references: Nature. 1997 Sep 18;389(6648):239-42
references: 9305836
references: Nat Rev Drug Discov. 2009 Feb;8(2):129-38
references: 19180106
references: Int J Nanomedicine. 2011;6:1793-800
references: 21980242
references: Proc Natl Acad Sci U S A. 2010 Feb 2;107(5):1864-9
references: 20080679
references: Proc Natl Acad Sci U S A. 2005 May 10;102(19):6839-42
references: 15863614
references: Langmuir. 2011 Sep 6;27(17):10962-9
references: 21728368
references: Nano Lett. 2009 Dec;9(12):4042-8
references: 19835370
references: Nano Lett. 2011 Sep 14;11(9):3720-6
references: 21793503
references: Angew Chem Int Ed Engl. 2008;47(44):8438-41
references: 18726979
references: J Am Chem Soc. 2010 Jun 23;132(24):8241-3
references: 20518524
references: Biomaterials. 2005 Jun;26(18):3995-4021
references: 15626447
references: Nat Mater. 2004 Dec;3(12):891-5
references: 15568032
references: Nat Biotechnol. 2000 Aug;18(8):893-5
references: 10932162
references: Q Rev Biophys. 2010 Feb;43(1):23-63
references: 20478077
references: Nat Nanotechnol. 2009 Sep;4(9):598-606
references: 19734934
references: Adv Enzyme Regul. 2001;41:189-207
references: 11384745
references: Biopolymers. 2007 Feb 5;85(2):115-30
references: 17103419
references: Langmuir. 2005 Jun 21;21(13):6006-18
references: 15952854
references: Angew Chem Int Ed Engl. 2003 Jul 14;42(27):3153-8
references: 12866105
references: Microvasc Res. 1984 May;27(3):353-69
references: 6727704