Inter-molecular ß-sheet structure facilitates lung-targeting siRNA delivery.
Sci Rep
; 6: 22731, 2016 Mar 09.
Article
em En
| MEDLINE
| ID: mdl-26955887
ABSTRACT
Size-dependent passive targeting based on the characteristics of tissues is a basic mechanism of drug delivery. While the nanometer-sized particles are efficiently captured by the liver and spleen, the micron-sized particles are most likely entrapped within the lung owing to its unique capillary structure and physiological features. To exploit this property in lung-targeting siRNA delivery, we designed and studied a multi-domain peptide named K-ß, which was able to form inter-molecular ß-sheet structures. Results showed that K-ß peptides and siRNAs formed stable complex particles of 60 nm when mixed together. A critical property of such particles was that, after being intravenously injected into mice, they further associated into loose and micron-sized aggregates, and thus effectively entrapped within the capillaries of the lung, leading to a passive accumulation and gene-silencing. The large size aggregates can dissociate or break down by the shear stress generated by blood flow, alleviating the pulmonary embolism. Besides the lung, siRNA enrichment and targeted gene silencing were also observed in the liver. This drug delivery strategy, together with the low toxicity, biodegradability, and programmability of peptide carriers, show great potentials in vivo applications.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Produtos Biológicos
/
Proteínas de Transporte
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RNA Interferente Pequeno
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Pulmão
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article