Agmatine-Containing Bioreducible Polymer for Gene Delivery Systems and Its Dual Degradation Behavior.

Abstract:

:Agmatine-containing bioreducible polymer, poly(cystaminebis(acrylamide)-agmatine) (poly(CBA-AG)) was synthesized for gene delivery systems. It could form 200-300 nm sized and positively charged polyplexes with pDNA, which could release pDNA in reducing the environment due to the internal disulfide bonds cleavage. Poly(CBA-AG) also showed a spontaneous degradation behavior in aqueous condition in contrast to the backbone polymer, poly(cystaminebis(acrylamide)-diaminobutane) (poly(CBA-DAB)) lacking guanidine moieties, probably due to the self-catalyzed hydrolysis of internal amide bonds by guanidine moieties. The cytotoxicity of poly(CBA-AG) was cell-dependent but minimal. Poly(CBA-AG) exhibited highly enhanced transfection efficiency in comparison with poly(CBA-DAB) and even higher transfection efficiency than PEI25k. However, cellular uptake efficiency of the polyplexes did not show positive correlation with the transfection efficiency. Confocal microscopy observation revealed that pDNA delivered by poly(CBA-AG) was strongly accumulated in cell nuclei. These results suggested that high transfection efficiency of poly(CBA-AG) may be derived from the efficient pDNA localization in cell nuclei by guanidine moieties and that the polyplexes dissociation via self-catalyzed hydrolysis as well as disulfide bonds cleavage in cytosol also may facilitate the transfection process. Finally, poly(CBA-AG)/pJDK-apoptin polyplex showed a high anticancer activity induced by apoptosis, demonstrating a potential of poly(CBA-AG) as a gene carrier for cancer gene therapy.

journal_name

Biomacromolecules

journal_title

Biomacromolecules

authors

Choi JY,Ryu K,Lee GJ,Kim K,Kim TI

doi

10.1021/acs.biomac.5b00590

subject

Has Abstract

pub_date

2015-09-14 00:00:00

pages

2715-25

issue

9

eissn

1525-7797

issn

1526-4602

journal_volume

16

pub_type

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