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

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

Data_Sheet_1_Layered Double Hydroxide Nanomaterials Encapsulating Angelica gigas Nakai Extract for Potential Anticancer Nanomedicine.DOC

<p>We prepared hybrids consisting of Angelica gigas Nakai (AGN) root or flower extract and layered double hydroxide (LDH) for potential anticancer nanomedicine, as decursin species (DS) in AGN are known to have anticancer activity. Dimethylsulfoxide solvent was determined hybridization reaction media, as it has affinity to both AGN and LDH moiety. In order to develop inter-particle spaces in LDH, a reversible dehydration-rehydration, so-called reconstruction route, was applied in AGN-LDH hybridization. Quantitative analyses on AGN-LDH hybrids indicated that the content of DS was two times more concentrated in the hybrids than in extract itself. Using X-ray diffraction, FT-IR spectroscopy, scanning electron microscopy, and zeta-potential measurement, we found that AGN extract moiety was incorporated into inter-particle spaces of LDH nanoparticles during the reconstruction reaction. Time-dependent DS release from hybrids at pH 7.4 (physiological condition) and pH 4.5 (lysosomal condition) exhibited a pH-dependent release of extract-incorporated LDH hybrids. An anticancer activity test using HeLa, A549, and HEK293T cells showed that the AGN-LDH hybrid, regardless of extract type, showed enhanced anticancer activity compared with extract alone at an equivalent amount of DS, suggesting a nanomedicine effect of AGN-LDH hybrids.</p