title: Uptake and transport of superparamagnetic iron oxide nanoparticles through human brain capillary endothelial cells.
abstract: The blood-brain barrier (BBB) formed by brain capillary endothelial cells (BCECs) constitutes a firm physical, chemical, and immunological barrier, making the brain accessible to only a few percent of potential drugs intended for treatment inside the central nervous system. With the purpose of overcoming the restraints of the BBB by allowing the transport of drugs, siRNA, or DNA into the brain, a novel approach is to use superparamagnetic iron oxide nanoparticles (SPIONs) as drug carriers. The aim of this study was to investigate the ability of fluorescent SPIONs to pass through human brain microvascular endothelial cells facilitated by an external magnet. The ability of SPIONs to penetrate the barrier was shown to be significantly stronger in the presence of an external magnetic force in an in vitro BBB model. Hence, particles added to the luminal side of the in vitro BBB model were found in astrocytes cocultured at a remote distance on the abluminal side, indicating that particles were transported through the barrier and taken up by astrocytes. Addition of the SPIONs to the culture medium did not negatively affect the viability of the endothelial cells. The magnetic force-mediated dragging of SPIONs through BCECs may denote a novel mechanism for the delivery of drugs to the brain.
authors.affiliation: Department of Health Science and Technology, Aalborg University , Aalborg, Denmark.
authors.forename: L B
authors.initials: LB
authors.lastname: Thomsen
authors.forename: T
authors.initials: T
authors.lastname: Linemann
authors.forename: K M
authors.initials: KM
authors.lastname: Pondman
authors.forename: J
authors.initials: J
authors.lastname: Lichota
authors.forename: K S
authors.initials: KS
authors.lastname: Kim
authors.forename: R J
authors.initials: RJ
authors.lastname: Pieters
authors.forename: G M
authors.initials: GM
authors.lastname: Visser
authors.forename: T
authors.initials: T
authors.lastname: Moos
mesh_terms: D001253:Astrocytes / Q000737:chemistry / Q000378:metabolism; D001693:Biological Transport, Active; D001812:Blood-Brain Barrier / Q000737:chemistry* / Q000166:cytology / Q000378:metabolism; D001921:Brain / Q000098:blood supply* / Q000166:cytology / Q000378:metabolism; D002199:Capillary Permeability; D002478:Cells, Cultured; D018920:Coculture Techniques; D063132:Connectome; D016503:Drug Delivery Systems / Q000379:methods; D004730:Endothelium, Vascular / Q000737:chemistry* / Q000166:cytology / Q000378:metabolism*; D005290:Ferric Compounds / Q000737:chemistry* / Q000378:metabolism; D005456:Fluorescent Dyes / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D008833:Microcirculation; D008959:Models, Neurological
chemical_list: D005290:Ferric Compounds; D005456:Fluorescent Dyes; D058185:Magnetite Nanoparticles; C000499:ferric oxide
references.citation: J Neurochem. 2010 Apr;113(1):1-13
references.pmid: 20015155
references.citation: Biochem Biophys Res Commun. 2010 Apr 16;394(4):871-6
references.pmid: 20206605
references.citation: J Control Release. 2012 Nov 28;164(1):49-57
references.pmid: 23063548
references.citation: J Cell Biol. 1969 Mar;40(3):648-77
references.pmid: 5765759
references.citation: Cancer Res. 1996 Oct 15;56(20):4694-701
references.pmid: 8840986
references.citation: Brain Res Rev. 2010 Sep 24;64(2):328-63
references.pmid: 20685221
references.citation: Biomaterials. 2008 Feb;29(4):487-96
references.pmid: 17964647
references.citation: Nanomedicine. 2010 Feb;6(1):64-9
references.pmid: 19446653
references.citation: Infect Immun. 1998 Nov;66(11):5260-7
references.pmid: 9784531
references.citation: Pharm Res. 2010 Nov;27(11):2283-95
references.pmid: 20845067
references.citation: Int J Nanomedicine. 2010 Apr 07;5:157-66
references.pmid: 20463931
references.citation: Int J Nanomedicine. 2011;6:373-80
references.pmid: 21499427
references.citation: Chem Rev. 2013 Mar 13;113(3):1877-903
references.pmid: 23157552
references.citation: Hum Gene Ther. 2003 Aug 10;14(12):1181-91
references.pmid: 12908969
references.citation: Gene Ther. 2002 Jan;9(2):102-9
references.pmid: 11857068
references.citation: Int J Nanomedicine. 2010 Nov 16;5:983-9
references.pmid: 21187917
references.citation: Biomaterials. 2008 Oct;29(29):4012-21
references.pmid: 18649936
references.citation: Biotechnol Adv. 2011 Jan-Feb;29(1):142-55
references.pmid: 20959138
references.citation: J Cereb Blood Flow Metab. 2004 Nov;24(11):1193-204
references.pmid: 15545912
references.citation: J Colloid Interface Sci. 1999 Jan 1;209(1):66-71
references.pmid: 9878137
references.citation: ACS Nano. 2011 Sep 27;5(9):7263-76
references.pmid: 21838310
references.citation: PLoS One. 2012;7(1):e29997
references.pmid: 22253854
references.citation: J Am Chem Soc. 2011 Mar 2;133(8):2525-34
references.pmid: 21288025
references.citation: J Neurosci Methods. 2011 Jan 15;194(2):287-96
references.pmid: 21074565
references.citation: Expert Opin Drug Deliv. 2009 Mar;6(3):227-37
references.pmid: 19327042
references.citation: Int J Nanomedicine. 2011;6:425-35
references.pmid: 21499432
references.citation: J Mater Sci Mater Med. 2009 Jan;20(1):301-7
references.pmid: 18791664
references.citation: Biofactors. 2010 Mar-Apr;36(2):103-10
references.pmid: 20232345
references.citation: Cell Mol Neurobiol. 2005 Feb;25(1):59-127
references.pmid: 15962509
references.citation: Methods Mol Biol. 2006;341:1-15
references.pmid: 16799185
references.citation: Mol Pharm. 2012 Jun 4;9(6):1620-7
references.pmid: 22536790
references.citation: Nature. 1984 Nov 8-14;312(5990):162-3
references.pmid: 6095085
references.citation: J Am Chem Soc. 2010 Apr 28;132(16):5761-8
references.pmid: 20356039
references.citation: Curr Pharm Biotechnol. 2004 Dec;5(6):567-84
references.pmid: 15579045
references.citation: Phys Rev E Stat Nonlin Soft Matter Phys. 2006 Jun;73(6 Pt 1):061919
references.pmid: 16906876