Reconstructed chitosan with alkylamine for enhanced gene delivery by promoting endosomal escape.
Carbohydr Polym
; 227: 115339, 2020 Jan 01.
Article
em En
| MEDLINE
| ID: mdl-31590870
ABSTRACT
Poor buffering capacity of chitosan (CS) results in insufficient intracellular gene release which poses the major barrier in gene delivery. Herein, we reconstructed pristine CS with propylamine (PA), (diethylamino) propylamine (DEAPA), and N, N-dimethyl- dipropylenetriamine (DMAMAPA) to obtain a series of alkylamine-chitosan (AA-CS). The introduction of multiple amino groups with rational ratios functionally enhance the buffering capacity of AA-CS, among which DMAPAPA-CS showed buffering capacity of 1.58 times that of chitosan. The reconstructed AA-CS functionally enhance the ability of gene binding and endosomal escape. It was observed that the DMAPAPA-CS/pDNA complexes exhibit a notable gene delivery efficiency, which promotes the functionalization of loaded pDNA. Importantly, the in vivo delivery assay reveals that the deep penetration issue can be resolved using DMAPAPA-CS gene delivery vector. Finally, the DMAPAPA-CS is applied to deliver the therapeutic p53 gene in A549 bearing mice, showing efficient therapeutic potential for cancer.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Endossomos
/
DNA
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Proteína Supressora de Tumor p53
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Técnicas de Transferência de Genes
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RNA Interferente Pequeno
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Quitosana
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Aminas
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Carbohydr Polym
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China