کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
11352 | 734 | 2008 | 9 صفحه PDF | دانلود رایگان |
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.
Journal: Biomaterials - Volume 29, Issue 2, January 2008, Pages 238–246