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A leptin derived 30-amino-acid peptide modified pegylated poly-l-lysine dendrigraft for brain targeted gene delivery

Paper ID Volume ID Publish Year Pages File Format Full-Text
8388 588 2010 12 PDF Available
Title
A leptin derived 30-amino-acid peptide modified pegylated poly-l-lysine dendrigraft for brain targeted gene delivery
Abstract

The blood–brain barrier is the major obstacle that prevents diagnostic and therapeutic drugs being delivered to the central nervous systems in order to exert their effects. Specific ligand-receptor binding mediated endocytosis is one of the possible strategies to cross this barrier. A 30-amino-acid peptide (leptin30) derived from an endogenic hormone—leptin is exploited as brain-targeting ligand as it is reported to possess the same brain accumulation efficiency after intravenous injection. Dendrigraft poly-l-lysine (DGL) is used as non-viral gene vector in this study. DGL–PEG–Leptin30 was complexed with plasmid DNA yielding nanoparticles (NPs). The cellular uptake characteristic and mechanism were explored in brain capillary endothelial cells (BCECs) which express leptin receptors. Furthermore, brain parenchyma microglia cells such as BV-2 cells expressing leptin receptors could promote ligand-receptor mediated endocytosis leading to enhanced gene transfection ability of DGL–PEG–Leptin30/DNA NPs. The targeted NPs were proved to be transported across in vitro BBB model effectively and accumulate more in brains after i.v. resulting in a relatively high gene transfection efficiency both in vitro and in vivo. Besides, the NPs showed low cytotoxicity after in vitro transfection. Thus, DGL–PEG–Leptin30 provides a safe and noninvasive approach for the delivery of gene across the blood–brain barrier.

Keywords
Brain targeting; Gene delivery; Leptin; Non-viral vector; Dendrigraft poly-l-lysine
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A leptin derived 30-amino-acid peptide modified pegylated poly-l-lysine dendrigraft for brain targeted gene delivery
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 31, Issue 19, July 2010, Pages 5246–5257
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