A nanoparticle system specifically designed to deliver short interfering RNA inhibits tumor growth in vivo.
Cancer Res
; 69(16): 6531-8, 2009 Aug 15.
Article
em En
| MEDLINE
| ID: mdl-19654315
Use of short interfering RNA (siRNA) is a promising new approach thought to have a strong potential to lead to rapid development of gene-oriented therapies. Here, we describe a newly developed, systemically injectable siRNA vehicle, the "wrapsome" (WS), which contains siRNA and a cationic lipofection complex in a core that is fully enveloped by a neutral lipid bilayer and hydrophilic polymers. WS protected siRNA from enzymatic digestion, providing a long half-life in the systemic circulation. Moreover, siRNA/WS leaked from blood vessels within tumors into the tumor tissue, where it accumulated and was subsequently transfected into the tumor cells. Because the transcription factor KLF5 is known to play a role in tumor angiogenesis, we designed KLF5-siRNA to test the antitumor activity of siRNA/WS. KLF5-siRNA/WS exhibited significant antitumor activity, although neither WS containing control scrambled-siRNA nor saline containing KLF5-siRNA affected tumor growth. KLF5-siRNA/WS inhibited Klf5 expression within tumors at both mRNA and protein levels, significantly reducing angiogenesis, and we detected no significant acute or long-term toxicity. Our findings support the idea that siRNA/WS can be used to knock down specific genes within tumors and thereby exert therapeutic effects against cancers.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sistemas de Liberação de Medicamentos
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RNA Interferente Pequeno
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Proliferação de Células
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Nanopartículas
/
Neoplasias
Tipo de estudo:
Diagnostic_studies
/
Evaluation_studies
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Prognostic_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Cancer Res
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Japão
País de publicação:
Estados Unidos