title: An in vitro and in vivo study of peptide-functionalized nanoparticles for brain targeting: The importance of selective blood-brain barrier uptake.
abstract: Targeted delivery of drugs across endothelial barriers remains a formidable challenge, especially in the case of the brain, where the blood-brain barrier severely limits entry of drugs into the central nervous system. Nanoparticle-mediated transport of peptide/protein-based drugs across endothelial barriers shows great potential as a therapeutic strategy in a wide variety of diseases. Functionalizing nanoparticles with peptides allows for more efficient targeting to specific organs. We have evaluated the hemocompatibilty, cytotoxicity, endothelial uptake, efficacy of delivery and safety of liposome, hyperbranched polyester, poly(glycidol) and acrylamide-based nanoparticles functionalized with peptides targeting brain endothelial receptors, in vitro and in vivo. We used an ELISA-based method for the detection of nanoparticles in biological fluids, investigating the blood clearance rate and in vivo biodistribution of labeled nanoparticles in the brain after intravenous injection in Wistar rats. Herein, we provide a detailed report of in vitro and in vivo observations.
authors.affiliation: Department of Neuroscience, School for Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands.
authors.forename: Gerard H
authors.initials: GH
authors.lastname: Bode
authors.affiliation: Department of Biomedical Chemistry, MIRA Institute for Biomedical Technology & Technical Medicine, Faculty of Science and Technology, University of Twente, The Netherlands.
authors.forename: Gregory
authors.initials: G
authors.lastname: Coué
authors.affiliation: REPAIR-lab, Institute of Pathology, University Medical Center of the Johannes Gutenberg University Mainz and European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Langenbeckstrasse 1, D-55101 Mainz, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Freese
authors.affiliation: HEALTH - Institute for Biomedicine and Health Sciences, Joanneum Research Forschungsgesellschaft m.b.H., Graz, Austria.
authors.forename: Karin E
authors.initials: KE
authors.lastname: Pickl
authors.affiliation: Grup d'Enginyeria de Materials (GEMAT), Institut Químic de Sarrià, Universitat Ramon Llull, Via Augusta 390, 08017 Barcelona, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Sanchez-Purrà
authors.affiliation: Grup d'Enginyeria de Materials (GEMAT), Institut Químic de Sarrià, Universitat Ramon Llull, Via Augusta 390, 08017 Barcelona, Spain.
authors.forename: Berta
authors.initials: B
authors.lastname: Albaiges
authors.affiliation: Grup d'Enginyeria de Materials (GEMAT), Institut Químic de Sarrià, Universitat Ramon Llull, Via Augusta 390, 08017 Barcelona, Spain.
authors.forename: Salvador
authors.initials: S
authors.lastname: Borrós
authors.affiliation: Regulon AE, Koropi, Athens, Greece.
authors.forename: Ewoud C
authors.initials: EC
authors.lastname: van Winden
authors.affiliation: N. C.S.R. "Demokritos", Institute of Nanoscience and Nanotechnology, 15310 Aghia Paraskevi, Attiki, Greece.
authors.forename: Leto-Aikaterini
authors.initials: LA
authors.lastname: Tziveleka
authors.affiliation: N. C.S.R. "Demokritos", Institute of Nanoscience and Nanotechnology, 15310 Aghia Paraskevi, Attiki, Greece.
authors.forename: Zili
authors.initials: Z
authors.lastname: Sideratou
authors.affiliation: Department of Biomedical Chemistry, MIRA Institute for Biomedical Technology & Technical Medicine, Faculty of Science and Technology, University of Twente, The Netherlands.
authors.forename: Johan F J
authors.initials: JFJ
authors.lastname: Engbersen
authors.affiliation: DWI-Leibniz Institute for Interactive Materials, RWTH Aachen University, Forckenbeckstr. 50, 52074 Aachen, Germany.
authors.forename: Smriti
authors.initials: S
authors.lastname: Singh
authors.affiliation: Department of Functional Materials in Medicine and Dentistry, University of Würzburg, Pleicherwall 2, 97070 Würzburg, Germany.
authors.forename: Krystyna
authors.initials: K
authors.lastname: Albrecht
authors.affiliation: Department of Functional Materials in Medicine and Dentistry, University of Würzburg, Pleicherwall 2, 97070 Würzburg, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Groll
authors.affiliation: DWI-Leibniz Institute for Interactive Materials, RWTH Aachen University, Forckenbeckstr. 50, 52074 Aachen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Möller
authors.affiliation: AplaGen GmbH, Arnold-Sommerfeld-Ring 2, D-52499 Baesweiler, Germany.
authors.forename: Andy J G
authors.initials: AJG
authors.lastname: Pötgens
authors.affiliation: Department of Neuroanatomy, Ludwig-Maximilians-University of Munich, Pettenkoferstrasse 11, 80336, Munich, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Schmitz
authors.affiliation: Center for Medical Research, Medical University of Graz, Graz, Austria.
authors.forename: Eleonore
authors.initials: E
authors.lastname: Fröhlich
authors.affiliation: Interfacultary Biomaterial Center (CEIB), University of Liege, Belgium.
authors.forename: Christian
authors.initials: C
authors.lastname: Grandfils
authors.affiliation: HEALTH - Institute for Biomedicine and Health Sciences, Joanneum Research Forschungsgesellschaft m.b.H., Graz, Austria.
authors.forename: Frank M
authors.initials: FM
authors.lastname: Sinner
authors.affiliation: REPAIR-lab, Institute of Pathology, University Medical Center of the Johannes Gutenberg University Mainz and European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Langenbeckstrasse 1, D-55101 Mainz, Germany.
authors.forename: C James
authors.initials: CJ
authors.lastname: Kirkpatrick
authors.affiliation: Department of Neuroscience, School for Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands.
authors.forename: Harry W M
authors.initials: HWM
authors.lastname: Steinbusch
authors.affiliation: Department of Neuroanatomy, Ludwig-Maximilians-University of Munich, Pettenkoferstrasse 11, 80336, Munich, Germany.
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Frank
authors.affiliation: REPAIR-lab, Institute of Pathology, University Medical Center of the Johannes Gutenberg University Mainz and European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Langenbeckstrasse 1, D-55101 Mainz, Germany.
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Unger
authors.affiliation: Department of Neuroscience, School for Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands. Electronic address: p.martinez@maastrichtuniversity.nl.
authors.forename: Pilar
authors.initials: P
authors.lastname: Martinez-Martinez
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002460:Cell Line; D004337:Drug Carriers; D016503:Drug Delivery Systems; D006801:Humans; D008081:Liposomes / Q000032:analysis / Q000378:metabolism* / Q000493:pharmacokinetics; D008297:Male; D053758:Nanoparticles / Q000032:analysis / Q000378:metabolism*; D010455:Peptides / Q000032:analysis / Q000378:metabolism* / Q000493:pharmacokinetics; D017208:Rats, Wistar; D014018:Tissue Distribution
chemical_list: D004337:Drug Carriers; D008081:Liposomes; D010455:Peptides
keywords: Brain; Nanoparticles; Peptides; Targeting