A novel DDS strategy, "dual-targeting", and its application for antineovascular therapy

Cancer Lett. 2010 Jan 28;287(2):165-71. doi: 10.1016/j.canlet.2009.06.008. Epub 2009 Jul 17.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / chemistry
  • Angiogenesis Inhibitors / pharmacokinetics
  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Antibiotics, Antineoplastic / administration & dosage
  • Antibiotics, Antineoplastic / chemistry
  • Antibiotics, Antineoplastic / pharmacokinetics
  • Antibiotics, Antineoplastic / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Chemistry, Pharmaceutical
  • Cholesterol / chemistry
  • Colonic Neoplasms / blood supply
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • Dose-Response Relationship, Drug
  • Doxorubicin / administration & dosage
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacokinetics
  • Doxorubicin / pharmacology*
  • Endothelial Cells / drug effects*
  • Endothelial Cells / metabolism
  • Humans
  • Injections, Intravenous
  • Liposomes
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Microscopy, Confocal
  • Oligopeptides / chemistry
  • Oligopeptides / metabolism*
  • Particle Size
  • Phosphatidylcholines / chemistry
  • Phosphatidylethanolamines / chemistry
  • Polyethylene Glycols / chemistry
  • Tissue Distribution

Substances

  • Angiogenesis Inhibitors
  • Antibiotics, Antineoplastic
  • Liposomes
  • Oligopeptides
  • Phosphatidylcholines
  • Phosphatidylethanolamines
  • alanyl-prolyl-arginyl-prolyl-glycine
  • 1,2-distearoylphosphatidylethanolamine
  • Polyethylene Glycols
  • Doxorubicin
  • Cholesterol
  • 1,2-distearoyllecithin