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

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.

• Authors: Won Jong Kim, James W Yockman, Ji Hoon Jeong, Lane V Christensen, Minhyung Lee, Yong-Hee Kim, Sung Wan Kim
• Journal: Journal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 114 Issue 3 Pg. 381-8 (Sep 12 2006) ISSN: 0168-3659 [Print] Netherlands
• PMID: 16884805 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• 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, 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)