Cyclic RGD-poly(ethylene glycol)-polyethyleneimine is more suitable for glioblastoma targeting gene transfer in vivo.

Abstract

Arginine-glycine-aspartic acid (RGD) is a widely chosen ligand to improve the specific gene targeting transfection efficiency of polyethyleneimine (PEI) in vivo. However, the optimal RGD conjugating mode, RGD-poly(ethylene glycol)-PEI (RGD-PEG-PEI) or RGD-PEI-methoxyl poly(ethylene glycol) (RGD-PEI-mPEG) still remains controversial. In this study, RGD-PEG-PEI and RGD-PEI-mPEG were synthesized and compared with respects to their glioblastoma cell-binding capability and tumor-targeting ability of their complexes with plasmid DNA. These results demonstrated that RGD-PEG-PEI/plasmid enhanced green fluorescent protein (pEGFP)-N2 complexes had higher binding affinities with U87 cells than RGD-PEI-mPEG/pEGFP-N2 complexes. The gene transfection was also performed on U87 cells in vitro and in vivo. In vitro, both of the RGD-modified PEI derivatives enhanced the gene transfection efficiency to some extent. However, all of the complexes (with or without RGD modification) had high transfection efficiency. The biodistribution of RGD-PEG-PEI/pEGFP-N2 complexes in mice bearing subcutaneous glioblastomas were significantly greater than that of RGD-PEI-mPEG/pEGFP-N2 complexes, suggesting a more efficient gene transfection in vivo. In the RGD-PEG-PEI, the use of a PEG spacer was particularly important. These results indicated that RGD-PEG-PEI was more suitable for targeted gene transfer in vivo.

• Authors: Changyou Zhan, Jun Qian, Linglin Feng, Gaoren Zhong, Jianhua Zhu, Weiyue Lu
• Journal: Journal of drug targeting (J Drug Target) Vol. 19 Issue 7 Pg. 573-81 (Aug 2011) ISSN: 1029-2330 [Electronic] England
• PMID: 21166603 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Peptides, Cyclic
• cyclic arginine-glycine-aspartic acid peptide
• Polyethylene Glycols
• Polyethyleneimine

Topics

• Animals
• Brain Neoplasms (genetics, pathology)
• Cell Line, Tumor
• Gene Transfer Techniques
• Glioblastoma (genetics, pathology)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Peptides, Cyclic (chemistry, pharmacokinetics)
• Polyethylene Glycols (chemistry, pharmacokinetics)
• Polyethyleneimine (chemistry, pharmacokinetics)