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The biocompatibility of fatty acid modified dextran-agmatine bioconjugate gene delivery vector

Paper ID Volume ID Publish Year Pages File Format Full-Text
7625 558 2012 10 PDF Available
Title
The biocompatibility of fatty acid modified dextran-agmatine bioconjugate gene delivery vector
Abstract

A lauric acid modified dextran-agmatine bioconjugate (Dex-l-Agm) was prepared by 1,1′-carbonyldiimidazole (CDI) activation and the nucleophilic reaction between tosyl of tosylated dextran and primary amine of agmatine. Dextran-agmatine bioconjugates (Dex-Agm) were capable of condensing DNA into nanocomplexes, and combining lauric acid promoted the complexation with DNA supposedly due to the cooperative binding effect attributed to hydrophobic interaction. Higher degree substitution of agmatine and hydrophobic grafting resulted in increased luciferase activities expressed in COS-7 and HEK293 cells; Semiquantitative assay of GFP expression by flow cytometry in COS-7, HEK293 and CHOK1 cells further demonstrated that conjugation of fatty acid could remarkably increase gene transfection of Dex-Agm in spite of 1.1–2.3-fold lower efficiency compared to Exgen 500. The biocompatibilities of Dex-Agm and Dex-l-Agm were assessed in detail by hemolytic activity determination, red blood cell aggregation assay as well as MTT evaluation of degraded products. Dex-Agm and Dex-l-Agm were shown to be highly cytocompatible without causing hemolysis and red blood cell aggregation presumably owing to the bidentate hydrogen bonding of guanidine with the constituents present in cell membrane rather than electrostatic interactions alone which could cause cell damage. Importantly, cells cultured with the degraded products of Dex-Agm and Dex-l-Agm retained more than 80% viability, suggest their potential application as a gene delivery vector.

Keywords
Dextran; Agmatine; Lauric acid; Hydrophobic modification; Gene transfection
First Page Preview
The biocompatibility of fatty acid modified dextran-agmatine bioconjugate gene delivery vector
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 33, Issue 2, January 2012, Pages 604–613
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering