PEGylation potentiates hepatoma cell targeted liposome-mediated in vitro gene delivery via the asialoglycoprotein receptor.
Z Naturforsch C J Biosci
; 72(7-8): 293-301, 2017 Jul 14.
Article
en En
| MEDLINE
| ID: mdl-28063265
ABSTRACT
Hepatocellular carcinoma is a burgeoning health issue in sub-Saharan Africa and East Asia where it is most prevalent. The search for gene medicine treatment modalities for this condition represents a novel departure from current treatment options and is gaining momentum. Here we report on nonPEGylated and on sterically stabilized PEGylated cationic liposomes decorated with D-galacto moieties linked to 24.1 Å spacers for asialoglycoprotein receptor (ASGP-R)-targeted vehiculation of pCMV-luc plasmid DNA. Cargo DNA is fully liposome associated at N/P ratio=31 and is partially protected from the effects of serum nucleases. Moreover, at this ratio, lipoplex dimensions (89-97 nm) are compatible with the requirements for extravasation in vivo. Ethidium displacement assays show that the reporter DNA is in a less condensed state when bound to PEGylated liposomes than with nonPEGylated liposomes. PEGylated lipoplexes were well tolerated by both HEK293 (ASGP-R-negative) and HepG2 (ASGP-R-positive) cell lines and delivered DNA to the human hepatoma cell line HepG2 by ASGP-R mediation at levels three-fold greater than nonPEGylated lipoplexes. PEGylated ASGP-R-targeted liposomes reported in this study possess the required characteristics for hepatotropic gene delivery and may be considered for further application in vivo.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Polietilenglicoles
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Técnicas de Transferencia de Gen
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Receptor de Asialoglicoproteína
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Liposomas
Límite:
Humans
Idioma:
En
Revista:
Z Naturforsch C J Biosci
Año:
2017
Tipo del documento:
Article
País de afiliación:
Sudáfrica
Pais de publicación:
ALEMANHA
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ALEMANIA
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DE
/
DEUSTCHLAND
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GERMANY