Combined Delivery of a Lipopolysaccharide-Binding Peptide and the Heme Oxygenase-1 Gene Using Deoxycholic Acid-Conjugated Polyethylenimine for the Treatment of Acute Lung Injury.
Macromol Biosci
; 17(8)2017 08.
Article
en En
| MEDLINE
| ID: mdl-28508430
A ternary complex comprising plasmid DNA, lipopolysaccharide-binding peptide (LBP), and deoxycholic acid-conjugated polyethylenimine (PEI-DA) is prepared for combinational therapy of acute lung injury (ALI). The LBP is designed as an anti-inflammatory peptide based on the lipopolysaccharide (LPS)-binding domain of HMGB-1. In vitro cytokine assays show that LBP reduces levels of proinflammatory cytokines by inhibiting LPS. PEI-DA is synthesized as the gene carrier by conjugation of deoxycholic acid to low-molecular weight polyethylenimine (2 kDa, PEI2k). PEI-DA has higher transfection efficiency than high-molecular weight polyethylenimine (25 kDa, PEI25k). The ternary complex of an HO-1 plasmid (pHO-1), PEI-DA, and LBP is prepared as a combinational system to deliver the therapeutic gene and peptide. The transfection efficiency of the ternary complex is higher than that of the pHO-1/PEI-DA binary complex. The ternary complex also reduces TNF-α secretion in LPS-activated Raw264.7 macrophage cells. Administration of the ternary complex into the lungs of an animal ALI model by intratracheal injection induces HO-1 expression and reduces levels of proinflammatory cytokines more efficiently than the pHO-1/PEI-DA binary complex or LBP alone. In addition, the ternary complex reduces inflammation in the lungs. Therefore, the pHO-1/PEI-DA/LBP ternary complex may be an effective treatment for ALI.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Polietileneimina
/
Proteínas de Fase Aguda
/
Glicoproteínas de Membrana
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Proteínas Portadoras
/
Técnicas de Transferencia de Gen
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Ácido Desoxicólico
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Hemo-Oxigenasa 1
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Lesión Pulmonar Aguda
/
Proteínas de la Membrana
Límite:
Animals
Idioma:
En
Revista:
Macromol Biosci
Asunto de la revista:
BIOQUIMICA
Año:
2017
Tipo del documento:
Article
País de afiliación:
Corea del Sur
Pais de publicación:
Alemania