Effective targeted gene delivery to dendritic cells via synergetic interaction of mannosylated lipid with DOPE and BCAT.
Biomacromolecules
; 13(3): 636-44, 2012 Mar 12.
Article
en En
| MEDLINE
| ID: mdl-22229467
ABSTRACT
The efficient delivery of plasmids encoding antigenic determinants into dendritic cells (DCs) that control immune response is a promising strategy for rapid development of new vaccines. In this study, we prepared a series of targeted cationic lipoplex based on two synthetic lipid components, mannose-poly(ethylene glycol, MW3000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (Mannose-PEG3000-DSPE) and O-(2R-1,2-di-O-(1'Z-octadecenyl)-glycerol)-3-N-(bis-2-aminoethyl)-carbamate (BCAT), that were formulated with 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) for evaluation as nonviral vectors for transgene expression in DCs. First, we optimized the N/P ratio for maximum transfection and then screened the effects of mannose targeting for further enhancement of transfection levels. Our results indicate that efficient delivery of gWIZ GFP plasmid into DCs was observed for mannose compositions of â¼10%, whereas low transfection efficiencies were observed with nontargeted formulations. Mannose-targeted lipofectamine complexes also showed high GFP expression levels in DCs relative to nontargeted lipofectamine controls. The best transfection performance was observed using 10 mol % Mannose-PEG3000-DSPE, 60 mol % BCAT, and 30 mol % DOPE, indicating that the most efficient delivery into DCs occurs via synergistic interaction between mannose targeting and acid-labile, fusogenic BCAT/DOPE formulations. Our data suggest that mannose-PEG3000-DSPE/BCAT/DOPE formulations may be effective gene delivery vehicles for the development of DC-based vaccines.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Fosfatidiletanolaminas
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Plásmidos
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Células Dendríticas
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Terapia Genética
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Proteínas Fluorescentes Verdes
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Lípidos
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Manosa
Límite:
Animals
Idioma:
En
Revista:
Biomacromolecules
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos