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Improving chitosan-mediated gene transfer by the introduction of intracellular buffering moieties into the chitosan backbone

Paper ID Volume ID Publish Year Pages File Format Full-Text
1111 76 2009 12 PDF Available
Title
Improving chitosan-mediated gene transfer by the introduction of intracellular buffering moieties into the chitosan backbone
Abstract

Chitosan was functionalized with imidazole moieties (CHimi) with the aim of improving its buffering capacity and promoting the endosomal escape ability of chitosan–DNA complexes, ultimately increasing their transfection efficiency. 5.6%, 12.9% and 22.1% of the glucosamine residues of chitosan were substituted. Complexes with different molar ratios of primary amines to DNA phosphate anion (N/P) were prepared by a coacervation method. For an N/P > 3, CHimi polymers are able to complex electrostatically with DNA and condense it into positively charged nanostructures (average size 260 nm and zeta potential +16 mV at pH 5.5). In the concentration range 2.5–100 μg ml−1, the modified polymers had no cytotoxic effect on 293T cells. CHimi polymers with the highest degree of substitution were found to enhance β-gal expression in 293T and HepG2 cells. Bafilomycin A1 inhibited transfection, indicating that the protonation of the imidazole groups in the endolysosome pathway favors the escape of the complexes from the endosomes, increasing the amount of transgene that can reach the cell nucleus.

Keywords
Chitosan; Nanoparticle; Gene delivery; Tissue engineering
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Improving chitosan-mediated gene transfer by the introduction of intracellular buffering moieties into the chitosan backbone
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Publisher
Database: Elsevier - ScienceDirect
Journal: Acta Biomaterialia - Volume 5, Issue 8, October 2009, Pages 2995–3006
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