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Relationships between chemical composition, physical properties and transfection efficiency of polysaccharide–spermine conjugates

Paper ID Volume ID Publish Year Pages File Format Full-Text
11577 747 2006 10 PDF Available
Title
Relationships between chemical composition, physical properties and transfection efficiency of polysaccharide–spermine conjugates
Abstract

Biodegradable water-soluble polysaccharide–spermine (SPM) polycation conjugates for nucleic acid delivery were synthesized by oxidizing polysaccharides using potassium periodate, followed by SPM conjugation. The polycations differ in their polysaccharide type, arabinogalactan (AG) or dextran (D), and/or in the IO4-IO4-/saccharide mole ratio used for polysaccharide oxidation (1:1, 1:3, or 1:5), resulting in either D(1:1)–SPM, AG(1:1)–SPM, D(1:3)–SPM, AG(1:3)–SPM, or AG(1:5)–SPM. Chemical structure of the conjugates was characterized for total nitrogen and primary amino groups. Surface pH and electrical surface potential were determined by means of spectral changes of covalently attached 7-hydroxycoumarin (HC, a pH- and electrical surface potential-sensitive fluorophore). The binding and the electrostatic neutralization of the polycations by plasmid DNA, as well as the relationship between chemical structure, physical parameters, and transfection of NIH3T3 cells, were also studied. D(1:1)–SPM, the only polycation that showed efficient cell transfection in culture, was shown to have: (1) high SPM content (2000 nmol/mg); (2) high levels of cross-linked SPM (39–51%); (3) at DNA P−/NH3+ ratio of 2.0, a plateau in neutralization of cationic groups (+48 mV, as determined by HC-labeled D(1:1)–SPM titration with DNA), and a drop in zeta-potential from +42 mV for the polymer alone to 0 mV for the polyplex, suggesting that some of the charges are hidden from the DNA; (4) pHsurface value of 9.2, suggesting that at physiological bulk pH the polymer is only partially ionized, and therefore can act as a “proton sponge” in the endosome; and (5) high sensitivity to serum-rich growth medium. An oleyl derivative, N-oleyl-dextran–spermine (ODS), was synthesized and demonstrated improved transfection efficiency in serum-rich medium.

Keywords
Gene delivery; Dextran; Fluorescence; Proton sponge
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Relationships between chemical composition, physical properties and transfection efficiency of polysaccharide–spermine conjugates
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 27, Issue 8, March 2006, Pages 1646–1655
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