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Bioreducible BPEI-SS-PEG-cNGR polymer as a tumor targeted nonviral gene carrier

Paper ID Volume ID Publish Year Pages File Format Full-Text
9296 624 2010 11 PDF Available
Title
Bioreducible BPEI-SS-PEG-cNGR polymer as a tumor targeted nonviral gene carrier
Abstract

The work demonstrated development of multifunctional gene carrier which has incorporated reducible moiety, tumor targeting ligands as well as PEG to achieve efficient release of pDNA, enhanced tumor-specificity and long circulation, respectively. In our successful one-pot synthesis of multifunctional polymer, low molecular weight branched polyethylenimine (BPEI) was thiolated with propylene sulfide, and mixed with α-Maleimide-ω-N-hydroxysuccinimide ester polyethylene glycol (MAL–PEG–NHS, MW: 5000), and cyclic NGR peptide. The structural elucidation of the cNGR conjugated reducible BPEI containing disulfide bond (BPEI-SS-PEG-cNGR), was done by NMR and GPC study. Complex formation as well as reducible property of the polymer was confirmed by gel retardation assay. In order to achieve efficient tumor targeting, we have used cNGR peptide which is known to bind to CD13 overexpressed in neovasculature endothelial cells. Tumor target-specificity of polymer was established by carrying out competitive inhibition assay with free cNGR peptide. Cellular uptake of polymers was evaluated by confocal laser scanning microscope (CLSM). Finally, addition of free cNGR and buthionine sulfoximine (BSO) reduced transfection efficiency synergistically, which implied that multifunctional polymer-mediated gene transfection took place tumor-specifically and via GSH-dependent pathway.

Keywords
NGR peptide; Polyethylenimine; Reducible; Tumor targeting; Gene delivery
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 31, Issue 24, August 2010, Pages 6344–6354
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