期刊
BIOMATERIALS
卷 30, 期 25, 页码 4195-4202出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2009.02.051
关键词
Brain targeting; Gene delivery; GABA(B) receptor; RVG; Non-viral vector; Polyamidoamine
资金
- National Basic Research Program of China (973 Program) [2007CB935802]
A 29 amino-acid peptide derived from the rabies virus glycoprotein (RVG29) was exploited as a ligand for efficient brain-targeting gene delivery. RVG29 was modified on polyamidoamine dendrimers (PAMAM) through bifunctional PEG, then complexed with DNA, yielding PAMAM-PEG-RVG29/DNA nanoparticles (NPs). The NPs were observed to be uptaken by brain capillary endothelial cells (BCECs) through a clathrin and caveolae mediated energy-depending endocytosis. The specific cellular uptake can be inhibited by free RVG29 and GABA but not by nicotinic acetylcholine receptor (nAchR) agonists/antagonists, indicating RVG29 probably relates to the GABA(B) receptor besides nAchR reported previously. PAMAM/DNA-PEG-RVG29/DNA NPs showed higher blood-brain barrier (BBB)-crossing efficiency than PAMAM/DNA NPs in an in vitro BBB model. In vivo imaging showed that the NPs were preferably accumulated in brain. The report gene expression of the PAMAM-PEG-RVG29/DNA NPs was observed in brain, and significantly higher than unmodified NPs. Thus, PAMAM-PEG-RVG29 provides a safe and noninvasive approach for the gene delivery across the BBB. (C) 2009 Elsevier Ltd. All rights reserved.
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