Amphiphilic poly(α)glutamate polymeric micelles for systemic administration of siRNA to tumors.
Nanomedicine
; 14(2): 303-315, 2018 02.
Article
en En
| MEDLINE
| ID: mdl-29127036
ABSTRACT
RNAi therapeutics carried a great promise to the area of personalized medicine the ability to target "undruggable" oncogenic pathways. Nevertheless, their efficient tumor targeting via systemic administration had not been resolved yet. Amphiphilic alkylated poly(α)glutamate amine (APA) can serve as a cationic carrier to the negatively-charged oligonucleotides. APA polymers complexed with siRNA to form round-shaped, homogenous and reproducible nano-sized polyplexes bearing ~50 nm size and slightly negative charge. In addition, APAsiRNA polyplexes were shown to be potent gene regulators in vitro. In light of these preferred physico-chemical characteristics, their performance as systemically-administered siRNA nanocarriers was investigated. Intravenously-injected APAsiRNA polyplexes accumulated selectively in tumors and did not accumulate in the lungs, heart, liver or spleen. Nevertheless, the polyplexes failed to induce specific mRNA degradation, hence neither reduction in tumor volume nor prolonged mice survival was seen.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Ácido Poliglutámico
/
Polímeros
/
Neoplasias de la Mama
/
ARN Interferente Pequeño
/
Tratamiento con ARN de Interferencia
/
Micelas
/
Antineoplásicos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Nanomedicine
Asunto de la revista:
BIOTECNOLOGIA
Año:
2018
Tipo del documento:
Article
País de afiliación:
Israel