RVG-peptide-linked trimethylated chitosan for delivery of siRNA to the brain.
Biomacromolecules
; 15(3): 1010-8, 2014 Mar 10.
Article
em En
| MEDLINE
| ID: mdl-24547943
ABSTRACT
In this work, a peptide derived from the rabies virus glycoprotein (RVG) was linked to siRNA/trimethylated chitosan (TMC) complexes through bifunctional PEG for efficient brain-targeted delivery of siRNA. The physiochemical properties of the complexes, such as siRNA complexing ability, size and ζ potential, morphology, serum stability, and cytotoxicity, were investigated prior to studying the cellular uptake, in vitro gene silencing efficiency, and in vivo biodistribution. The RVG-peptide-linked siRNA/TMC-PEG complexes showed increased serum stability, negligible cytotoxicity, and higher cellular uptake than the unmodified siRNA/TMC-mPEG complexes in acetylcholine receptor positive Neuro2a cells. The potent knockdown of BACE1, a therapeutic target in Alzheimer's disease, demonstrated the gene silencing efficiency. In vivo imaging analysis showed significant accumulation of Cy5-siRNA in the isolated brain of mice injected with RVG-peptide-linked complexes. Therefore, the RVG-peptide-linked TMC-PEG developed in this study can be used as a potential carrier for delivery of siRNA to the brain.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
/
Proteínas Virais
/
Glicoproteínas
/
Terapia Genética
/
Ácido Aspártico Endopeptidases
/
Técnicas de Transferência de Genes
/
RNA Interferente Pequeno
/
Secretases da Proteína Precursora do Amiloide
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Biomacromolecules
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
China