Bioreducible branched poly(modified nona-arginine) cell-penetrating peptide as a novel gene delivery platform.
J Control Release
; 246: 142-154, 2017 01 28.
Article
em En
| MEDLINE
| ID: mdl-27170226
ABSTRACT
Cell-penetrating peptides (CPPs) have been widely used to deliver nucleic acid molecules. Generally, CPPs consisting of short amino acid sequences have a linear structure, resulting in a weak complexation and low transfection efficacy. To overcome these drawbacks, a novel type of CPP is required to enhance the delivery efficacy while maintaining its safe use at the same time. Herein, we report that a bioreducible branched poly-CPP structure capable of responding to reducing conditions attained both outstanding delivery effectiveness and selective gene release in carcinoma cells. Branched structures provide unusually strong electrostatic attraction between DNA and siRNA molecules, thereby improving the transfection capability through a tightly condensed form. We designed a modified type of nona-arginine (mR9) and synthesized a branched-mR9 (B-mR9) using disulfide bonds. A novel B-mR9/pDNA polyplex exhibited redox-cleavability and high transfection efficacy compared to conventional CPPs, with higher cell viability as well. B-mR9/VEGF siRNA polyplex exhibited significant serum stability and high gene-silencing effects in vitro. Furthermore, the B-mR9 polyplex showed outstanding tumor accumulation and inhibition ability in vivo. The results suggest that the bioreducible branched poly CPP has great potential as a gene delivery platform.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Arginina
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Plasmídeos
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DNA
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Técnicas de Transferência de Genes
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RNA Interferente Pequeno
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Peptídeos Penetradores de Células
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
J Control Release
Assunto da revista:
FARMACOLOGIA
Ano de publicação:
2017
Tipo de documento:
Article