Pegylated siRNA-loaded calcium phosphate nanoparticle-driven amplification of cancer cell internalization in vivo.
Biomaterials
; 34(12): 2980-90, 2013 Apr.
Article
em En
| MEDLINE
| ID: mdl-23369215
ABSTRACT
The cell membrane is a critical barrier to effective delivery for many therapeutics, including those which are nanoparticle-based. Improving nanoparticle transport across the cell membrane remains a fundamental challenge. Cancer cells preferentially internalized pegylated calcium phosphate nanoparticles over normal epithelial cells. Furthermore, non-cytotoxic levels of doxorubicin markedly amplified this difference by increasing free unbound caveolin-1 and resulted in enhanced caveolin-mediated nanoparticle endocytosis in cancer cells. Engineered pegylated siRNA-loaded triple-shell calcium phosphate nanoconstructs incorporating ultra-low levels of doxorubicin recapitulated these effects and delivered increased numbers of siRNA into cancer cells with target-specific results. Systemic administration of nanoparticles in vivo demonstrated highly preferential entry into tumors, little bystander organ biodistribution, and significant tumor growth arrest. In conclusion, siRNA-loaded calcium phosphate nanoparticles incorporating non-cytotoxic amounts of doxorubicin markedly enhances nanoparticle internalization and results in increased payload delivery with concomitant on-target effects.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Polietilenoglicóis
/
Fosfatos de Cálcio
/
RNA Interferente Pequeno
/
Endocitose
/
Nanopartículas
/
Neoplasias
Limite:
Humans
Idioma:
En
Revista:
Biomaterials
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos