title: RGDfK-functionalized gold nanorods bind only to activated platelets.
abstract: Integrin-targeting peptide RGDfK-labeled gold nanorods (GNR) seek to improve hyperthermia targeted to solid tumors by exploiting the known up-regulation of integrin αvβ3 cell membrane proteins on solid tumor vasculature surfaces. Tumor binding specificity might be expected since surrounding tissues and endothelial cells have limited numbers of these receptors. However, RGD peptide binding to many proteins is promiscuous, with known affinity to several families of cell integrin receptors, and also possible binding to platelets after intravenous infusion via a different integrin receptor, αIIbβ3, on platelets. Binding of RGDfK-targeted GNR could considerably impact platelet function, ultimately leading to increased risk of bleeding or thrombosis depending on the degree of interaction. We sought to determine if RGDfK-labeled GNR could interact with platelets and alter platelet function. Targeted and untargeted nanorods exhibited little interaction with resting platelets in platelet rich plasma (PRP) preparations. However, upon platelet activation, peptide-targeted nanorods bound actively to platelets. Addition of RGDfK-GNR to unactivated platelets had little effect on markers of platelet activation, indicating that RGDfK-nanorods were incapable of inducing platelet activation. We next tested whether activated platelet function was altered in the presence of peptide-targeted nanorods. Platelet aggregation in whole blood and PRP in the presence of targeted nanorods had no significant effect on platelet aggregation. These data suggest that RGDfK-GNR alone have little impact on platelet function in plasma. However, nonspecific nanorod binding may occur in vascular beds where activated platelets are normally cleared, such as the spleen and liver, producing a possible toxicity risk for these nanomaterials. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 209-217, 2017.
authors.affiliation: Department of Pharmaceutics and Pharmaceutical Chemistry, Health Sciences, University of Utah, Salt Lake City, Utah, 84112.
authors.forename: Krystin
authors.initials: K
authors.lastname: Zeller Meidell
authors.affiliation: Department of Bioengineering, University of Utah, Salt Lake City, Utah, 84112.|Center for Nanomedicine, Nano Institute of Utah, University of Utah, Salt Lake City, Utah, 84112.
authors.forename: Ryan
authors.initials: R
authors.lastname: Robinson
authors.affiliation: Program in Molecular Medicine, School of Medicine, University of Utah, Salt Lake City, Utah, 84112.
authors.forename: Adriana
authors.initials: A
authors.lastname: Vieira-de-Abreu
authors.affiliation: Department of Bioengineering, University of Utah, Salt Lake City, Utah, 84112.|Center for Nanomedicine, Nano Institute of Utah, University of Utah, Salt Lake City, Utah, 84112.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Gormley
authors.affiliation: Department of Pharmaceutics and Pharmaceutical Chemistry, Health Sciences, University of Utah, Salt Lake City, Utah, 84112.|Department of Bioengineering, University of Utah, Salt Lake City, Utah, 84112.|Center for Nanomedicine, Nano Institute of Utah, University of Utah, Salt Lake City, Utah, 84112.
authors.forename: Hamidreza
authors.initials: H
authors.lastname: Ghandehari
authors.affiliation: Department of Pharmaceutics and Pharmaceutical Chemistry, Health Sciences, University of Utah, Salt Lake City, Utah, 84112.|Department of Bioengineering, University of Utah, Salt Lake City, Utah, 84112.|Center for Nanomedicine, Nano Institute of Utah, University of Utah, Salt Lake City, Utah, 84112.
authors.forename: David
authors.initials: D
authors.lastname: W Grainger
authors.affiliation: Program in Molecular Medicine, School of Medicine, University of Utah, Salt Lake City, Utah, 84112.
authors.forename: Robert
authors.initials: R
authors.lastname: A Campbell
mesh_terms: D000328:Adult; D001792:Blood Platelets / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D006046:Gold / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008297:Male; D053768:Metal Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D043942:Nanotubes / Q000737:chemistry* / Q000648:ultrastructure; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology; D015539:Platelet Activation / Q000187:drug effects*
chemical_list: D009842:Oligopeptides; C084961:arginyl-glycyl-aspartyl-phenylalanine; D006046:Gold
keywords: activation; blood clot; coagulation; integrin; nanoparticles; peptide ligand