NDLI: In vitro and in vivo platelet targeting by cyclic RGD-modified liposomes.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Srinivasan, Rekha Marchant, Roger E. Gupta, Anirban Sen
Description	Country affiliation: United States Author Affiliation: Srinivasan R ( Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106, USA.)
Abstract	Cell-selective delivery using ligand-decorated nanoparticles is a promising modality for treating cancer and vascular diseases. We are developing liposome nanoparticles surface-modified by RGD peptide ligands having targeting specificity to integrin GPIIb-IIIa. This integrin is upregulated and stimulated into a ligand-binding conformation on the surface activated platelets. Activated-platelet adhesion and aggregation are primary events in atherosclerosois, thrombosis, and restenosis. Hence, platelet-targeted nanoparticles hold the promise of vascular site-selective delivery of drugs and imaging probes. Here, we report in vitro and ex vivo microscopy studies of platelet-targeting by liposomes surface-modified with a cyclic RGD peptide. The peptide-modified liposomes were labeled either with a lipophilic fluorophore or with lipid-tethered Nanogold(R). For in vitro tests, coverslip-adhered activated human platelets were incubated with probe-labeled liposomes, followed by analysis with fluorescence microscopy, phase contrast microscopy, and scanning electron microscopy (SEM). For in vivo tests, the liposomes were introduced within a catheter-injured carotid artery restenosis model in rats and post-euthanasia, the artery was imaged ex vivo by fluorescence microscopy and SEM. All microscopy results showed successful platelet-targeting by the peptide-modified liposomes. The in vitro SEM results also enabled visualization of nanoscopic liposomes attached to activated platelets. The results validate our nanoparticle design for site-selective vascular delivery.
File Format	HTM / HTML
ISSN	15493296
e-ISSN	15524965
DOI	10.1002/jbm.a.32549
Journal	Journal of Biomedical Materials Research Part A
Issue Number	3
Volume Number	93
Language	English
Publisher	Wiley
Publisher Date	2010-06-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Research Support, N.i.h., Extramural Carotid Arteries Blood Platelets Cytology Pharmacology Nanostructures Metabolism Drug Effects Drug Delivery Systems Discipline Biomedical Engineering Peptides, Cyclic Pathology Chemistry Animals Flow Cytometry Ultrastructure Liposomes Microscopy, Fluorescence Disease Models, Animal
Content Type	Text
Resource Type	Article
Subject	Ceramics and Composites Metals and Alloys Biomaterials Biomedical Engineering

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