title: Peptide-targeted PEG-liposomes in anti-angiogenic therapy.
abstract: Peptides with the RGD amino acid sequence show affinity for the alpha(v)beta(3) integrin, an integrin which is over-expressed on angiogenic endothelium and involved in cell adhesion. A peptide with the sequence ATWLPPR has been demonstrated to show affinity for the vascular endothelial growth factor (VEGF) receptor, a receptor involved in the proliferation of endothelial cells. By coupling these peptides to liposomes, these liposomes can serve as a site-specific drug delivery system to tumor endothelial cells in order to inhibit angiogenesis. In the present study we demonstrate that the coupling of cyclic RGD-peptides or ATWLPPR-peptides to the surface of PEG-liposomes results in binding of these liposomes to endothelial cells in vitro. Subsequent studies with RGD-peptide targeted liposomes in vivo also demonstrate specific binding to the tumor endothelium.
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht, The Netherlands.
authors.forename: A P C A
authors.initials: AP
authors.lastname: Janssen
authors.forename: R M
authors.initials: RM
authors.lastname: Schiffelers
authors.forename: T L M
authors.initials: TL
authors.lastname: ten Hagen
authors.forename: G A
authors.initials: GA
authors.lastname: Koning
authors.forename: A J
authors.initials: AJ
authors.lastname: Schraa
authors.forename: R J
authors.initials: RJ
authors.lastname: Kok
authors.forename: G
authors.initials: G
authors.lastname: Storm
authors.forename: G
authors.initials: G
authors.lastname: Molema
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy / Q000378:metabolism; D002478:Cells, Cultured; D004337:Drug Carriers; D016503:Drug Delivery Systems; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry / Q000295:instrumentation / Q000379:methods; D006801:Humans; D066298:In Vitro Techniques; D008081:Liposomes / Q000737:chemistry; D051379:Mice; D018613:Microscopy, Confocal / Q000295:instrumentation / Q000379:methods; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D009842:Oligopeptides / Q000737:chemistry*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism; D013997:Time Factors; D019737:Transplants
chemical_list: D020533:Angiogenesis Inhibitors; D004337:Drug Carriers; D008081:Liposomes; D009842:Oligopeptides; D010446:Peptide Fragments; D011092:Polyethylene Glycols; C047981:arginyl-glycyl-aspartic acid; D040262:Receptors, Vascular Endothelial Growth Factor