The use of lactoferrin as a ligand for targeting the polyamidoamine-based gene delivery system to the brain.
Development of an efficient gene vector is a key-limiting factor of brain gene therapy. In this study, lactoferrin (Lf), for the first time, was investigated as a brain-targeting ligand in the design of polyamidoamine (PAMAM)-based non-viral gene vector to the brain. Using polyethyleneglycol (PEG) as a spacer, PAMAM-PEG-Lf was successfully synthesized. This vector showed a concentration-dependent manner in the uptake in brain capillary endothelial cells (BCECs). The brain uptake of PAMAM-PEG-Lf was 2.2-fold compared to that of PAMAM-PEG-transferrin (Tf) in vivo. The transfection efficiency of PAMAM-PEG-Lf/DNA complex was higher than that of PAMAM-PEG-Tf/DNA complex in vitro and in vivo. The results of frozen sections showed the widespread expression of an exogenous gene in mouse brain via intravenous administration. With a PAMAM/DNA weight ratio of 10:1, the brain gene expression of the PAMAM-PEG-Lf/DNA complex was about 2.3-fold when compared to that of the PAMAM-PEG-Tf/DNA complex. These results provide evidence that PAMAM-PEG-Lf can be exploited as a potential non-viral gene vector targeting to the brain via noninvasive administration. Lf is a promising ligand for the design of gene delivery systems targeting to the brain.
Huang
Rongqin
R
Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 200032, PR China.
Ke
Weilun
W
Liu
Yang
Y
Jiang
Chen
C
Pei
Yuanying
Y
D000818:Animals; D001921:Brain; D002478:Cells, Cultured; D042783:Endothelial Cells; D015870:Gene Expression; D018014:Gene Transfer Techniques; D007781:Lactoferrin / Q000737:chemistry*; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008807:Mice, Inbred BALB C; D011073:Polyamines / Q000737:chemistry*
D008024:Ligands; D011073:Polyamines; D007781:Lactoferrin