Aqueous-Soluble, Acid-Transforming Chitosan for Efficient and Stimuli-Responsive Gene Silencing.
Biomacromolecules
; 19(5): 1508-1516, 2018 05 14.
Article
en En
| MEDLINE
| ID: mdl-29562124
ABSTRACT
Despite its promises for biomedical applications, the lack of solubility in a physiological solution, the limited molecular interactions with nucleic acids due to the rigid backbone, and the inefficient intracellular release limit the use of chitosan, a natural cationic polysaccharide, for gene delivery. In this study, a flexible, aqueous-soluble aminoethoxy branch was conjugated to the primary hydroxyl group of chitosan via an acid-cleavable ketal linkage, resulting in acid-transforming chitosan (ATC) with greatly increased aqueous solubility, improved siRNA complexation, and degradability in response to an acidic pH. Acid-hydrolysis of ketal linkages, which triggers the loss of the flexible, cationic aminoethoxy branch, transforms ATC to the native form of chitosan with low water solubility, reduces molecular interaction with siRNA, and cooperatively facilitates the cytosolic release of siRNA. The siRNA complexation by ATC resulted in stable polyplexes under a neutral physiological condition, rapid cytosolic siRNA release from the mildly acidic endosome/lysosome, and substantial silencing of GFP expression in cells, notably with minimal cytotoxicity. This study demonstrates a molecularly engineered natural polymer for a biomedical application.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Transfección
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Silenciador del Gen
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ARN Interferente Pequeño
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Quitosano
Límite:
Humans
Idioma:
En
Revista:
Biomacromolecules
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2018
Tipo del documento:
Article