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Hydrolyzable p(DMAPEMA) Polymers for Gene Delivery
Author(s) -
Veron Laurent,
Ganée Arnaud,
Ladavière Catherine,
Delair Thierry
Publication year - 2006
Publication title -
macromolecular bioscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.924
H-Index - 105
eISSN - 1616-5195
pISSN - 1616-5187
DOI - 10.1002/mabi.200600071
Subject(s) - chemistry , transfection , polymer , cationic polymerization , dna , agarose gel electrophoresis , gene delivery , polymer chemistry , zeta potential , biophysics , methacrylate , hydrolysis , gel electrophoresis , biochemistry , organic chemistry , monomer , chemical engineering , gene , nanoparticle , biology , engineering
Summary: The efficiency of cationic polymers as transfectants is thought to be closely related to their DNA association/dissociation properties. An incomplete polymer‐DNA dissociation could explain the relatively low gene expression obtained with p(DMAEMA) polymers. Our approach was to synthesize a p(DMAEMA) analogue, p(DMAPEMA), bearing an hydrolyzable cationic group incorporated into the pendant chain with a view to improving transfection. The complexation of DNA with both polymers was studied by agarose gel electrophoresis, size and zeta potential measurements, as well as the dissociation of the polyplexes, after treatment by an anionic polymer, sodium hydroxide or heat. The transfection efficiencies of the polyplexes were evaluated with 293T and BHK21 cells in comparison with Exgen 500. P(DMAPEMA) polymers were able to complex DNA and to release it in a free intact form after an alkaline treatment or storage at 37 °C. Poly(aspartic acid) was unable to dissociate p(DMAPEMA) based polyplexes, in contrast to p(DMAEMA) ones. No transfection was obtained with p(DMAPEMA) with both cell lines. A slow hydrolysis under physiological conditions resulting in the absence of DNA unpacking or endosomal entrapment could explain these results. Better transfection results were obtained with polyplexes which were able to be dissociated by electrostatic interactions rather than ones which required the hydrolysis mechanism to release free DNA into cells.Scheme of hydrolyzable p(DMAPEMA) polymer.