Abstract
Dual-targeting liposomes modified with Ala-Pro-Arg-Pro-Gly (APRPG) and Gly-Asn-Gly-Arg-Gly (GNGRG) peptides were developed. They remarkably associated to growing human umbilical vein endothelial cells (HUVECs) compared with single-targeting liposomes modified with APRPG or GNGRG. Doxorubicin (DOX) encapsulated in the dual-targeting liposomes significantly suppressed the growth of HUVECs compared with that in single-targeting liposomes. The dual-targeting liposomes containing DOX strongly suppressed tumor growth in Colon26 NL-17 carcinoma-bearing mice. Confocal microscopic data indicated that this anticancer effect was brought by the association of these liposomes to angiogenic vessels in the tumor. These findings suggest that "dual-targeting" would be a hopeful method for targeting therapies.
Copyright 2009 Elsevier Ireland Ltd. All rights reserved.
Publication types
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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 / chemistry
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Angiogenesis Inhibitors / pharmacokinetics
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Angiogenesis Inhibitors / pharmacology*
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Animals
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Antibiotics, Antineoplastic / administration & dosage
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Antibiotics, Antineoplastic / chemistry
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Antibiotics, Antineoplastic / pharmacokinetics
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Antibiotics, Antineoplastic / pharmacology*
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Cell Line, Tumor
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Cell Proliferation / drug effects*
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Chemistry, Pharmaceutical
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Cholesterol / chemistry
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Colonic Neoplasms / blood supply
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Colonic Neoplasms / drug therapy*
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Colonic Neoplasms / metabolism
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Colonic Neoplasms / pathology
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Dose-Response Relationship, Drug
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Doxorubicin / administration & dosage
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Doxorubicin / chemistry
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Doxorubicin / pharmacokinetics
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Doxorubicin / pharmacology*
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Endothelial Cells / drug effects*
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Endothelial Cells / metabolism
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Humans
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Injections, Intravenous
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Liposomes
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Male
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Mice
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Mice, Inbred BALB C
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Microscopy, Confocal
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Oligopeptides / chemistry
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Oligopeptides / metabolism*
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Particle Size
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Phosphatidylcholines / chemistry
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Phosphatidylethanolamines / chemistry
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Polyethylene Glycols / chemistry
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Tissue Distribution
Substances
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Angiogenesis Inhibitors
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Antibiotics, Antineoplastic
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Liposomes
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Oligopeptides
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Phosphatidylcholines
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Phosphatidylethanolamines
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alanyl-prolyl-arginyl-prolyl-glycine
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1,2-distearoylphosphatidylethanolamine
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Polyethylene Glycols
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Doxorubicin
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Cholesterol
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1,2-distearoyllecithin