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.