title: Amphiphilic cationic carbosilane-PEG dendrimers: synthesis and applications in gene therapy.
abstract: 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.
authors.affiliation: Department of Química Orgánica y Química Inorgánica, Universidad de Alcalá, Campus Universitario, Alcalá de Henares, Madrid E-28871, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Sánchez-Nieves
authors.affiliation: Institute for Research in Biomedicine, Barcelona Science Park, Baldiri Reixac 10, 08028 Barcelona, Spain.
authors.forename: Peter
authors.initials: P
authors.lastname: Fransen
authors.affiliation: Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Spain; Combinatorial Chemistry Unit, Barcelona Science Park, Baldiri Reixac 10, 08028 Barcelona, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Pulido
authors.affiliation: Laboratorio de Inmunología Molecular, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Lorente
authors.affiliation: Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Spain; Laboratorio de Inmunología Molecular, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: M Ángeles
authors.initials: MÁ
authors.lastname: Muñoz-Fernández
authors.affiliation: Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Spain; Institute for Research in Biomedicine, Barcelona Science Park, Baldiri Reixac 10, 08028 Barcelona, Spain; Department of Organic Chemistry, University of Barcelona, Martí i Franqués 1-11, 08028 Barcelona, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Albericio
authors.affiliation: Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Spain; Combinatorial Chemistry Unit, Barcelona Science Park, Baldiri Reixac 10, 08028 Barcelona, Spain.
authors.forename: Miriam
authors.initials: M
authors.lastname: Royo
authors.affiliation: Department of Química Orgánica y Química Inorgánica, Universidad de Alcalá, Campus Universitario, Alcalá de Henares, Madrid E-28871, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Spain. Electronic address: rafael.gomez@uah.es.
authors.forename: Rafael
authors.initials: R
authors.lastname: Gómez
authors.affiliation: Department of Química Orgánica y Química Inorgánica, Universidad de Alcalá, Campus Universitario, Alcalá de Henares, Madrid E-28871, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Spain.
authors.forename: F Javier
authors.initials: FJ
authors.lastname: de la Mata
mesh_terms: D002412:Cations; D002851:Chromatography, High Pressure Liquid; D050091:Dendrimers / Q000737:chemistry*; D015316:Genetic Therapy; D015658:HIV Infections / Q000628:therapy; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D011092:Polyethylene Glycols / Q000737:chemistry*; D012821:Silanes / Q000737:chemistry*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D002412:Cations; D050091:Dendrimers; D012821:Silanes; C504072:carbosilane; D011092:Polyethylene Glycols
keywords: Carbosilane; Click chemistry; Dendrimers; Gene therapy; HIV; PEG