The use of lactoferrin as a ligand for targeting the polyamidoamine-based gene delivery system to the brain
The use of lactoferrin as a ligand for targeting the polyamidoamine-based gene delivery system to the brain
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DOI：
10.1016/j.biomaterials.2007.09.024
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发表时间：
2008-01-01
期刊：
影响因子：
14
通讯作者：
Pei, Yuanying
中科院分区：
文献类型：
--
作者：
Huang, Rongqin;Ke, Weilun;Pei, Yuanying
开发高效的基因载体是脑基因治疗的关键限制因素。在本研究中，首次将乳铁蛋白(LF)作为脑靶向配体用于设计基于聚酰胺胺(PAMAM)的非病毒脑内基因载体。以聚乙二醇作间隔物，成功地合成了PAMAM-PEG-LF。该载体对脑毛细血管内皮细胞(BCECs)的摄取呈浓度依赖性。体内对PAMAM-PEG-LF的脑摄取是Tf的2.2倍。PAMAM-PEG-LF/DNA复合体在体内外的转染率均高于PAMAM-PEG-Tf/DNA复合体。冰冻切片结果表明，外源基因通过静脉注射在小鼠脑内广泛表达。当PAMAM/DNA重量比为10：1时，PAMAM-PEG-LF/DNA复合体的脑基因表达约为PAMAM-PEG-Tf/DNA复合体的2.3倍。这些结果表明，PAMAM-PEG-LF可以作为一种潜在的非病毒基因载体，通过非侵入性给药靶向于脑内。Lf是一种很有前途的配体，可用于设计针对大脑的基因递送系统。(C)2007爱思唯尔有限公司。保留所有权利。
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. (C) 2007 Elsevier Ltd. All rights reserved.