Amphiphilic cationic carbosilane-PEG dendrimers: synthesis and applications in gene therapy

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 dendrim...

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Detalles Bibliográficos
Autores: Sánchez-Nieves, Javier, Fransen, Peter, Pulido, Daniel, Lorente, Raquel, Muñoz-Fernández, M. Ángeles, Albericio, Fernando, Royo, Miriam, Gómez, Rafael, de la Mata, F Javier
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2014
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/346194
Acceso en línea:http://hdl.handle.net/10261/346194
https://api.elsevier.com/content/abstract/scopus_id/84896706310
Access Level:acceso abierto
Palabra clave:PEG
Carbosilane
Click chemistry
Dendrimers
Gene therapy
HIV
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Descripción
Sumario: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.