Anti-angiogenic inhibition of tumor growth by systemic delivery of PEI-g-PEG-RGD/pCMV-sFlt-1 complexes in tumor-bearing mice

J Control Release. 2006 Sep 12;114(3):381-8. doi: 10.1016/j.jconrel.2006.05.029. Epub 2006 Jun 7.

Abstract

Vascular endothelial growth factor (VEGF) is an endogenous mediator of tumor angiogenesis. Blocking associations of the VEGF with its corresponding receptors (Flt-1, KDR/flk-1) have become critical for anti-tumor angiogenesis therapy. Previously, we synthesized PEI-g-PEG-RGD conjugate and evaluated as an angiogenic endothelial polymeric gene carrier. In this study, PEI-g-PEG-RGD/pCMV-sFlt-1 complexes are evaluated in terms of tumor growth inhibition in vivo. Complexes were repeatedly injected systemically via tail vein into subcutaneous tumor-bearing mice. As a result, tumor growth was inhibited in the PEI-g-PEG-RGD/pCMV-sFlt-1 injected group. However, this effect was not identified in PEI-g-PEG/pCMV-sFlt-1 or PEI-g-PEG-RGD/pCMV-GFP control groups. Moreover, the survival rate increased in the PEI-g-PEG-RGD/pCMV-sFlt-1 group compared with the controls group. These results suggest that delivery of pCMV-sFlt-1 using PEG-g-PEG-RGD may be effective for anti-angiogenic gene therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / administration & dosage*
  • Animals
  • Cell Line, Tumor
  • Cytomegalovirus / genetics
  • Drug Carriers
  • Female
  • Gene Transfer Techniques*
  • Genetic Therapy / methods*
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Neoplasms, Experimental / blood supply
  • Neoplasms, Experimental / drug therapy*
  • Peptides, Cyclic / administration & dosage*
  • Polyethylene Glycols / administration & dosage*
  • Tissue Distribution
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*
  • Vascular Endothelial Growth Factor Receptor-1 / genetics*

Substances

  • Angiogenesis Inhibitors
  • Drug Carriers
  • PEI-g-PEG-RGD
  • Peptides, Cyclic
  • Vascular Endothelial Growth Factor A
  • Polyethylene Glycols
  • Vascular Endothelial Growth Factor Receptor-1