title: In vitro studies of water-stable cationic carbosilane dendrimers as delivery vehicles for gene therapy against HIV and hepatocarcinoma.
abstract: Here we present a synthetic procedure for water-stable carbosilane dendrimers containing ammonium groups at the periphery of type Gn-{[Si(CH2)3N+(Me)(Et)CH2CH2N+Me3]x (CF3SO3 -)y} which have been used as non-viral vectors for transfecting different types of nucleic acids against two different medical problems, HIV and hepatocarcinoma. These systems have shown to be non-toxic in both PBMC and HepG2 cell lines under the experimental conditions and are able to form nanoconjugates with nucleic acids perfectly stable over time and in a wide range of pH values, which leads to the conclusion that the interaction between dendrimer and nucleic acid is very strong. In addition, a high degree of transfection using these nanoconjugates has been observed, ranging from 70-90% depending on the generation and in the particular case of PBMC transfection with anti-HIV oligonucleotides. However, besides of the good properties shown by the dendrimers here prepared as transfecting agents, only moderate effect was observed in functional experiments for hepatocarcinoma, as a result of the strong interaction between dendrimer and nucleic acid. Nevertheless, it is important to mention that an IRS-4 knock-down of 40% in HepG2 achieves an analogous degree of cell sensitization to cancer treatment, which may represent a major advance in the hepatocarcinoma treatment when appropriate dendrimers as transfection agents are used.
authors.affiliation: Laboratorio de Inmunobiología Molecular, Hospital General Universitario Gregorio Marañón, Madrid Spain.
authors.forename: N
authors.initials: N
authors.lastname: de Las Cuevas
authors.forename: S
authors.initials: S
authors.lastname: Garcia-Gallego
authors.forename: B
authors.initials: B
authors.lastname: Rasines
authors.forename: F J
authors.initials: FJ
authors.lastname: de la Mata
authors.forename: L G
authors.initials: LG
authors.lastname: Guijarro
authors.forename: M Á
authors.initials: MÁ
authors.lastname: Muñoz-Fernández
authors.forename: R
authors.initials: R
authors.lastname: Gómez
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000628:therapy*; D002412:Cations / Q000008:administration & dosage / Q000737:chemistry; D050091:Dendrimers / Q000008:administration & dosage / Q000737:chemistry*; D015316:Genetic Therapy / Q000379:methods*; D015658:HIV Infections / Q000235:genetics / Q000628:therapy*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000628:therapy*; D012821:Silanes / Q000008:administration & dosage / Q000737:chemistry*; D014162:Transfection / Q000379:methods*
chemical_list: D002412:Cations; D050091:Dendrimers; D012821:Silanes; C504072:carbosilane