Abstract
Nuclease-resistant aptamers identified from randomized nucleic acid libraries represent a novel class of drug candidates. Aptamers are synthesized chemically and therefore can be readily modified with functional groups that modulate their properties. We report here on the preparation, initial characterization, and functional properties of a nuclease-resistant vascular endothelial growth factor (VEGF) aptamer anchored in liposome bilayers through a lipid group on the aptamer. While the high-affinity binding to VEGF is maintained, the plasma residence time of the liposome-anchored aptamer is considerably improved compared with that of the free aptamer. The lipid group attachment and/or liposome anchoring leads to a dramatic improvement in inhibitory activity of the aptamer toward VEGF-induced endothelial cell proliferation in vitro and vascular permeability increase and angiogenesis in vivo.
MeSH terms
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Animals
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Capillary Permeability / drug effects
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Cell Division / drug effects
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Cells, Cultured
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Endothelial Growth Factors / metabolism*
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Endothelium, Vascular / drug effects*
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Humans
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Liposomes / metabolism*
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Lymphokines / metabolism*
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Microscopy, Electron
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Molecular Structure
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Neovascularization, Physiologic / drug effects
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Oligonucleotides / pharmacology*
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Particle Size
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Protein Binding / drug effects
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Rats
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Rats, Sprague-Dawley
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Receptor Protein-Tyrosine Kinases / metabolism
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Receptors, Growth Factor / metabolism
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Receptors, Vascular Endothelial Growth Factor
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Ribonuclease T1 / metabolism
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
Substances
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Endothelial Growth Factors
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Liposomes
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Lymphokines
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Oligonucleotides
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Receptors, Growth Factor
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
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Receptor Protein-Tyrosine Kinases
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Receptors, Vascular Endothelial Growth Factor
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Ribonuclease T1