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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Bibliographic Details
Authors: Sánchez-Nieves Fernández, Javier|||0000-0003-0410-2285, Fransen, Peter, Pulido, Daniel, Llorente Heras, Raquel, Muñoz Fernández, María Ángeles, Albericio, Fernando, Royo, Miriam, Gómez Ramírez, Rafael|||0000-0001-6448-2414, Mata de la Mata, Francisco Javier de la|||0000-0003-0418-3935
Format: article
Publication Date:2014
Country:España
Institution:Universidad de Alcalá (UAH)
Repository:e_Buah Biblioteca Digital Universidad de Alcalá
Language:English
OAI Identifier:oai:ebuah.uah.es:10017/33945
Online Access:http://hdl.handle.net/10017/33945
https://dx.doi.org/10.1016/j.ejmech.2014.01.061
Access Level:Open access
Keyword:Dendrimers
Click chemistry
Carbosilane
PEG
Gene therapy
HIV
Química
Chemistry
Description
Summary: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.