Cationic derivatives of biocompatible hyaluronic acids for delivery of siRNA and antisense oligonucleotides.
J Drug Target
; 17(2): 123-32, 2009 Feb.
Article
en En
| MEDLINE
| ID: mdl-19012052
ABSTRACT
In this study, we tested the use of cationic polymer derivatives of biocompatible hyaluronic acid (HA) as a delivery system of siRNA and antisense oligonucleotides. HA was modified with cationic polymer polyethylenimine (PEI). When compared with PEI alone, cationic PEI derivatives of HA (HA-PEI) provided increased cellular delivery of Small interfering RNA (siRNA) in B16F1, A549, HeLa, and Hep3B tumor cells. Indeed, more than 95% of the cells were positive for siRNA following its delivery with HA-PEI. A survivin-specific siRNA that was delivered using HA-PEI potently reduced the mRNA expression levels of the target gene in all of the cell lines. By contrast, survivin-specific siRNA delivered by PEI alone did not induce a significant reduction in mRNA levels. In green fluorescent protein (GFP)-expressing 293 T cells, a loss of GFP expression was evident in the cells that had been treated with GFP-specific siRNA and HA-PEI complex. The inhibition of target gene expression by antisense oligonucleotide G3139 was also enhanced after delivery with HA-PEI. Moreover, HA-PEI displayed lower cytotoxicity than PEI alone. These results suggest that HA-PEI could be further developed as biocompatible delivery systems of siRNA and antisense oligonucleotides for enhanced cellular uptake and inhibition of target gene expression.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Oligonucleótidos Antisentido
/
ARN Interferente Pequeño
/
Ácido Hialurónico
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Drug Target
Asunto de la revista:
FARMACOLOGIA
Año:
2009
Tipo del documento:
Article
País de afiliación:
Corea del Sur