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.
Copyright 2002 Elsevier Science B.V.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Angiogenesis Inhibitors / administration & dosage*
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Angiogenesis Inhibitors / therapeutic use
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Animals
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Carcinoma, Lewis Lung / drug therapy
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Carcinoma, Lewis Lung / metabolism
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Cells, Cultured
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Drug Carriers
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Drug Delivery Systems*
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Endothelium, Vascular / drug effects
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Endothelium, Vascular / metabolism
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Flow Cytometry / instrumentation
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Flow Cytometry / methods
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Humans
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In Vitro Techniques
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Liposomes / chemistry
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Mice
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Microscopy, Confocal / instrumentation
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Microscopy, Confocal / methods
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Neovascularization, Pathologic / drug therapy
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Oligopeptides / chemistry*
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Peptide Fragments / administration & dosage
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Peptide Fragments / chemistry
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Polyethylene Glycols / chemistry*
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Receptors, Vascular Endothelial Growth Factor / metabolism
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Time Factors
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Transplants
Substances
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Angiogenesis Inhibitors
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Drug Carriers
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Liposomes
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Oligopeptides
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Peptide Fragments
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Polyethylene Glycols
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arginyl-glycyl-aspartic acid
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Receptors, Vascular Endothelial Growth Factor