Vascular endothelial growth factor-C siRNA delivered via calcium carbonate nanoparticle effectively inhibits lymphangiogenesis and growth of colorectal cancer in vivo.
Cancer Biother Radiopharm
; 24(2): 249-59, 2009 Apr.
Article
en En
| MEDLINE
| ID: mdl-19409048
ABSTRACT
A nonviral gene carrier, calcium carbonate (CaCO(3))-nanoparticle, was evaluated for the efficient in vitro and in vivo delivery of siRNA-targeting vascular endothelial growth factor-C (VEGF-C). The chemically synthesized CaCO(3)-nanoparticle has a 58-nm diameter and a + 28.6-mV positive surface charge. It is capable of forming a CaCO(3)-nanoparticle-DNA complex and transferring DNA into targeted cells with high transfection efficiency, while effectively protecting the encapsulated DNA from degradation. Further, the CaCO(3)-nanoparticle-DNA complex has no obvious cytotoxicity for LoVo cells, while a liposome-DNA complex exhibited measurable cytotoxicity. LoVo cells transfected with a VEGF-C-targeted small interfering RNA (siRNA) via the CaCO(3)-nanoparticle exhibits significantly reduced VEGF-C expression, as measured by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay, whereas no decrease in VEGF-C expression is observed in cells treated by control transfection. Transfection of LoVo cells with VEGF-C siRNA via the CaCO(3)-nanoparticle also dramatically suppresses tumor lymphangiogenesis, tumor growth, and regional lymph-node metastasis in subcutaneous xenografts. Significant downregulation of VEGF-C messenger RNA expression in a subcutaneous xenograft derived from VEGF-C siRNA-treated LoVo cells was confirmed by real-time PCR, as compared to controls. We conclude that the CaCO(3)-nanoparticle is a novel, nonviral system for the effective delivery of siRNA for cancer gene therapy.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Carbonato de Calcio
/
Neoplasias Colorrectales
/
Terapia Genética
/
ARN Interferente Pequeño
/
Factor C de Crecimiento Endotelial Vascular
/
Nanopartículas
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Cancer Biother Radiopharm
Asunto de la revista:
FARMACIA
/
FARMACOLOGIA
/
NEOPLASIAS
/
TERAPEUTICA
Año:
2009
Tipo del documento:
Article
País de afiliación:
China