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Brain-targeting gene delivery and cellular internalization mechanisms for modified rabies virus glycoprotein RVG29 nanoparticles

Paper ID Volume ID Publish Year Pages File Format Full-Text
9944 654 2009 8 PDF Available
Title
Brain-targeting gene delivery and cellular internalization mechanisms for modified rabies virus glycoprotein RVG29 nanoparticles
Abstract

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 GABAB receptor besides nAchR reported previously. PAMAM–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.

Keywords
Brain targeting; Gene delivery; GABAB receptor; RVG; Non-viral vector; Polyamidoamine
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Brain-targeting gene delivery and cellular internalization mechanisms for modified rabies virus glycoprotein RVG29 nanoparticles
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 30, Issue 25, September 2009, Pages 4195–4202
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us