Multivalent effects of RGD peptides obtained by nanoparticle display.
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.
Montet
Xavier
X
Department of Radiology, Geneva Hospital, Geneva, Switzerland, and Department of Angiography and Interventional Radiology, Vienna Medical University, Vienna, Austria.
Funovics
Martin
M
Montet-Abou
Karin
K
Weissleder
Ralph
R
Josephson
Lee
L
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
D039302:Integrin alphaVbeta3; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid