Targeted gene delivery to glioblastoma using a C-end rule RGERPPR peptide-functionalised polyethylenimine complex.

Abstract

Safe and efficient systems capable of specifically targeting brain tumour cells represent a promising approach for the treatment glioblastoma multiforme. Neuropilin-1 (NRP-1) is over-expressed in U87 glioma cells. In the current study, the tumour specific peptide RGERPPR, which binds specifically to NRP-1, was used as a targeting ligand in a gene delivery strategy for glioblastoma. The RGERPPR peptide was coupled to branched polyethylenimine (PEI, 25kDa) using heterobifunctional Mal-PEG-NHS, resulting in a novel gene delivery polymer. Polymer/plasmid DNA (pDNA) complexes were formed and their sizes and zeta potentials were measured. Compared with the unmodified mPEG-PEI/pDNA complexes, the RGERPPR-PEG-PEI/pDNA complex led to a significant enhancement in intracellular gene uptake and tumour spheroid penetration. Furthermore, the RGERPPR-PEG-PEI/pDNA complex facilitated enhanced transfection efficiency levels, as well as a reduction in cytotoxicity when tested in U87 glioma cells in vitro. Most significantly of all, when complexes formed with pDsRED-N1 were injected into the tail vein of intracranial U87 tumour-bearing nude mice, the RGERPPR-PEG-PEI complexes led to improved levels of red fluorescence protein expression in the brain tissue. Taken together, the results show that RGERPPR-PEG-PEI could be used as a safe and efficient gene delivery vehicle with potential applications in glioblastoma gene delivery.

• Authors: Jing Wang, Yang Lei, Cao Xie, Weiyue Lu, Zhiqiang Yan, Jie Gao, Zuoxu Xie, Xiaoyu Zhang, Min Liu
• Journal: International journal of pharmaceutics (Int J Pharm) Vol. 458 Issue 1 Pg. 48-56 (Dec 15 2013) ISSN: 1873-3476 [Electronic] Netherlands
• PMID: 24144951 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier B.V. All rights reserved.

Chemical References

• Peptides
• Polymers
• polypeptide C
• Neuropilin-1
• Polyethyleneimine
• DNA

Topics

• Animals
• Brain Neoplasms (drug therapy)
• Cell Line, Tumor
• DNA (administration & dosage)
• Gene Transfer Techniques
• Glioblastoma (drug therapy)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neuropilin-1 (metabolism)
• Particle Size
• Peptides (administration & dosage)
• Plasmids (administration & dosage)
• Polyethyleneimine (administration & dosage)
• Polymers (administration & dosage)
• Transfection (methods)