title: Multivalent effects of RGD peptides obtained by nanoparticle display.
abstract: The binding of RGD peptides to integrins offers an excellent system to study the multivalent mediated changes in affinity that arise when peptides, displayed on the surface of a nanoparticle carrier, bind to integrins displayed on the cell membrane. The IC50 of an RGD nanoparticle for endothelial adhesion was 1.0 nM nanoparticle or 20 nM peptide (20 peptide/nanoparticle) and was associated with strong multivalent effects, defined as a multivalent enhancement factor (MVE) of 38 (MVE=IC50 (peptide)/IC50 (peptide when displayed by nanoparticle)). The attachment of RGD peptides to nanoparticles resulted in an extension of the peptide blood half-life from 13 to 180 min. Based on the multivalent enhancement of affinity and extension of blood half-life, multivalent RGD nanoparticle-sized materials should be potent inhibitors of the alpha(V)beta(3) function on endothelial cells in vivo.
authors.affiliation: Department of Radiology, Geneva Hospital, Geneva, Switzerland, and Department of Angiography and Interventional Radiology, Vienna Medical University, Vienna, Austria.
authors.forename: Xavier
authors.initials: X
authors.lastname: Montet
authors.forename: Martin
authors.initials: M
authors.lastname: Funovics
authors.forename: Karin
authors.initials: K
authors.lastname: Montet-Abou
authors.forename: Ralph
authors.initials: R
authors.lastname: Weissleder
authors.forename: Lee
authors.initials: L
authors.lastname: Josephson
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D042783:Endothelial Cells / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology; D006207:Half-Life; D006801:Humans; D066298:In Vitro Techniques; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D049329:Nanostructures; D009842:Oligopeptides / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D039302:Integrin alphaVbeta3; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid