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A linear-dendritic cationic vector for efficient DNA grasp and delivery

Paper ID Volume ID Publish Year Pages File Format Full-Text
699 60 2012 12 PDF Available
Title
A linear-dendritic cationic vector for efficient DNA grasp and delivery
Abstract

This paper presents an attempt to design an efficient and biocompatible cationic gene vector via structural optimization that favors the efficient utilization of amine groups for DNA condensation. To this end, a linear-dendritic block copolymer of methoxyl-poly(ethylene glycol)-dendritic polyglycerol-graft-tris(2-aminoethyl)amine (mPEG-DPG-g-TAEA) was prepared with specially designed multiple functions including strong DNA affinity, endosomal buffering and expected serum-tolerance. Based on the transfection in serum-free and serum-conditioned media, the influences of the polymer structures including the degree of polymerization of DPG and TAEA substitution degree were explored. As compared to polyethylenimine (Mw = 5 kDa) (PEI5k) with similar molecular weight and higher amine density, mPEG-DPG-g-TAEA displayed comparably high DNA affinity due to the special linear-dendritic architecture. Consequently, at very low N/P ratio, mPEG-DPG-g-TAEA vectors could mediate efficient in vitro luciferase expression at levels that are comparable with or even superior to the commercially available Lipofectamine™ 2000, while being apparently higher than PEI5k. The designed vectors exhibit considerably higher cell biocompatibility and better resistance against bovine serum albumin adsorption than PEI5k. The stability of the complexes on coincubation with heparin was found to be largely dependent on the polymer structure. As concluded from the comparative transfection study in the absence/presence of chloroquine, it is likely that the polycation itself could produce endosomal buffering. This linear-dendritic vector shows promising potential for the application of gene delivery.

Keywords
Endosomal buffering; Gene delivery; Methoxyl-poly(ethylene glycol)-dendritic polyglycerol-g-tris(2-aminoethyl)amine (mPEG-DPG-g-TAEA); Cationic vector; Protein adsorption
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A linear-dendritic cationic vector for efficient DNA grasp and delivery
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Publisher
Database: Elsevier - ScienceDirect
Journal: Acta Biomaterialia - Volume 8, Issue 6, July 2012, Pages 2121–2132
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