Amphiphilic Cationic Carbosilane-PEG Dendrimers: Synthesis and Applications in Gene Therapy
Autores
Sánchez-Nieves Fernández, JavierIdentificadores
Enlace permanente (URI): http://hdl.handle.net/10017/33945DOI: 10.1016/j.ejmech.2014.01.061
ISSN: 0223-5234
Editor
Elsevier
Fecha de publicación
2014-01-31Patrocinadores
Comunidad de Madrid
Ministerio de Sanidad y Consumo
Ministerio de Economía y Empresa
Cita bibliográfica
European Journal of Medicinal Chemistry, 2014, v. 76 , p. 43-52
Palabras clave
Dendrimers
Click chemistry
Carbosilane
PEG
Gene therapy
HIV
Proyectos
PI061479 (Ministerio de Sanidad y Consumo)
RD06-0006-0035 (red Iris)
24632/07(FIPSE)
NAN2007-31198-E (MNT-ERA NET 2007)
S-SAL-0159-2006 (Comunidad de Madrid)
S2011/BMD-2351 (Comunidad de Madrid)
SAF2011-30508-C02-01 (Ministerio de Economía y Empresa)
Tipo de documento
info:eu-repo/semantics/article
Versión
info:eu-repo/semantics/acceptedVersion
Derechos
Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
(c) Elsevier, 2014
Derechos de acceso
info:eu-repo/semantics/openAccess
Resumen
Here we synthesized carbosilane, generation 1 to 3, and PEG-based dendrons functionalized at the periphery with NHBoc groups and at the focal point with azide and alkyne moieties, respectively. The coupling of these two types of dendrons via click chemistry led to the formation of new hybrid dendrimers with two distinct moieties, the hydrophobic carbosilane and the hydrophilic PEG-based dendron. The protected dendrimers were transformed into cationic ammonium dendrimers. These unique amphiphilic dendrimers were studied as vectors for gene therapy against HIV in peripheral blood mononuclear cells (PBMC) and their performance was compared with that of a PEG-free carbosilane dendrimer. The presence of the PEG moiety afforded lower toxicities and evidenced a weaker interaction between dendrimers and siRNA when compared to the homodendrimer analogous. Both features, lower toxicity and lower dendriplex strength, are key properties for use of these vectors as carriers of nucleic material.
Ficheros en el ítem
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amphiphilic_mata_ejmc_2014.pdf | 1.671Mb |
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amphiphilic_mata_ejmc_2014.pdf | 1.671Mb |
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