title: Targeting of peptide conjugated magnetic nanoparticles to urokinase plasminogen activator receptor (uPAR) expressing cells.
abstract: Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles are currently being used as a magnetic resonance imaging (MRI) contrast agent in vivo, mainly by their passive accumulation in tissues of interest. However, a higher specificity can ideally be achieved when the nanoparticles are targeted towards cell specific receptors and this may also facilitate specific drug delivery by an enhanced target-mediated endocytosis. We report efficient peptide-mediated targeting of magnetic nanoparticles to cells expressing the urokinase plasminogen activator receptor (uPAR), a surface biomarker for poor patient prognosis shared by several cancers including breast, colorectal, and gastric cancers. Conjugation of a uPAR specific targeting peptide onto polyethylene glycol (PEG) coated USPIO nanoparticles by click chemistry resulted in a five times higher uptake in vitro in a uPAR positive cell line compared to nanoparticles carrying a non-binding control peptide. In accordance with specific receptor-mediated recognition, a low uptake was observed in the presence of an excess of ATF, a natural ligand for uPAR. The uPAR specific magnetic nanoparticles can potentially provide a useful supplement for tumor patient management when combined with MRI and drug delivery.
authors.affiliation: Interdisciplinary Nanoscience Center (iNANO), Departments of Molecular Biology and Genetics, Physics and Astronomy, Aarhus University, DK-8000 Aarhus C, Denmark.
authors.forename: Line
authors.initials: L
authors.lastname: Hansen
authors.forename: Esben Kjær Unmack
authors.initials: EK
authors.lastname: Larsen
authors.forename: Erik Holm
authors.initials: EH
authors.lastname: Nielsen
authors.forename: Frank
authors.initials: F
authors.lastname: Iversen
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Liu
authors.forename: Karen
authors.initials: K
authors.lastname: Thomsen
authors.forename: Michael
authors.initials: M
authors.lastname: Pedersen
authors.forename: Troels
authors.initials: T
authors.lastname: Skrydstrup
authors.forename: Niels Chr
authors.initials: NC
authors.lastname: Nielsen
authors.forename: Michael
authors.initials: M
authors.lastname: Ploug
authors.forename: Jørgen
authors.initials: J
authors.lastname: Kjems
mesh_terms: D000595:Amino Acid Sequence; D057930:Click Chemistry; D005290:Ferric Compounds / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry; D057809:HEK293 Cells; D006801:Humans; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D018613:Microscopy, Confocal; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D011092:Polyethylene Glycols; D011485:Protein Binding; D055293:Receptors, Urokinase Plasminogen Activator / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D005290:Ferric Compounds; D005456:Fluorescent Dyes; D058185:Magnetite Nanoparticles; D010455:Peptides; D055293:Receptors, Urokinase Plasminogen Activator; C000499:ferric oxide; D011092:Polyethylene Glycols