Anti-angiogenic inhibition of tumor growth by systemic delivery of PEI-g-PEG-RGD/pCMV-sFlt-1 complexes in tumor-bearing mice.
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.
Kim
Won Jong
WJ
Center for Controlled Chemical Delivery, Department of Pharmaceutics and Pharmaceutical Chemistry, 20 S 2030 E RM 205 BPRB, University of Utah, Salt Lake City, UT 84112-5820, USA.
Yockman
James W
JW
Jeong
Ji Hoon
JH
Christensen
Lane V
LV
Lee
Minhyung
M
Kim
Yong-Hee
YH
Kim
Sung Wan
SW
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000818:Animals; D045744:Cell Line, Tumor; D003587:Cytomegalovirus / Q000235:genetics; D004337:Drug Carriers; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000098:blood supply / Q000188:drug therapy*; D010456:Peptides, Cyclic / Q000008:administration & dosage*; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D014018:Tissue Distribution; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics*
D020533:Angiogenesis Inhibitors; D004337:Drug Carriers; C507107:PEI-g-PEG-RGD; D010456:Peptides, Cyclic; D042461:Vascular Endothelial Growth Factor A; D011092:Polyethylene Glycols; D040281:Vascular Endothelial Growth Factor Receptor-1