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Polyhistidine–PEG:DNA nanocomposites for gene delivery

Paper ID Volume ID Publish Year Pages File Format Full-Text
13282 848 2003 9 PDF Available
Title
Polyhistidine–PEG:DNA nanocomposites for gene delivery
Abstract

Complexation of plasmid DNA with polycations is a popular method by which to transfer therapeutic nucleic acid sequences to cells. One caveat of the approach is that the positive zeta potential of the complexes facilitates interaction with blood constituents, leading to serum protein adsorption and complement activation. As a countermeasure, investigators have developed polycations combined with polyethylene glycol (PEG) to create complexes with reduced protein adsorption potential. We have designed and synthesized PEG–polyhistidine conjugates to evaluate the material class as potential gene delivery vehicles. Two conjugate architectures (comb-shaped and linear A–B block copolymers) were synthesized and formulated with plasmid DNA. The complexes were characterized with respect to DNA complexation capacity, hydrodynamic diameter, zeta potential, in vitro cytotoxicity and transfection capacity in a model cell line. PEG content of the conjugate significantly influenced the hydrodynamic diameter of the DNA:conjugate composite in aqueous solution. For comb-shaped conjugates steric hindrance attributed to PEG led to a direct relationship between the PEG content and the complex size. Both architectures could condensed plasmid DNA into complexes with hydrodynamic diameters <150 nm. Complexation of DNA with the polyhistidine–PEG conjugates resulted in nanocomposites with negative zeta potentials that retarded DNase I-mediated hydrolysis, and all conjugates showed low cytotoxicity to macrophages cultured in vitro. The transfection efficiency was approximately equivalent to DNA:polylysine complexes. The formulation characteristics and low cytotoxicity suggest that polyhistidine–PEG conjugates may be useful for gene delivery.

Keywords
Polyhistidine; Polyethylene glycol; Polymer architecture; DNA:polycation complexes; Gene delivery
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 24, Issue 24, November 2003, Pages 4425–4433
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