title: Water-soluble carbosilane dendrimers: synthesis biocompatibility and complexation with oligonucleotides; evaluation for medical applications.
abstract: Novel amine- or ammonium-terminated carbosilane dendrimers of type nG-[Si{OCH2(C6H3)-3,5-(OCH2CH2NMe2)2}]x, nG-[Si{O(CH2)2N(Me)(CH2)2NMe2}]x and nG-[Si{(CH2)3NH2}]x or nG-[Si{OCH2(C6H3)-3,5-(OCH2CH2NMe3 +I-)2}]x, nG-[Si{O(CH2)2N(Me)(CH2)2NMe3 +I-}]x, and nG-[Si{(CH2)3NH3 +Cl-}]x have been synthesized and characterized up to the third generation by two strategies: 1) alcoholysis of Si--Cl bonds with amino alcohols and subsequent quaternization with MeI, and 2) hydrosilylation of allylamine with Si--H bonds of the dendritic systems and subsequent quaternization with HCl. Quaternized carbosilane dendrimers are soluble in water, although degradation is apparent due to hydrolysis of Si--O bonds. However, dendrimers containing Si--C bonds are water-stable. The biocompatibility of the second-generation dendrimers in primary cell cultures of peripheral blood mononuclear cells (PBMCs) and erythrocytes have been analyzed, and they show good toxicity profiles over extended periods. In addition, we describe a study on the interactions between the different carbosilane dendrimers and DNA oligodeoxynucleotides (ODNs) and plasmids along with a comparative analysis of their toxicity. They can form complexes with DNA ODNs and plasmids at biocompatible doses via electrostatic interaction. Also a preliminary transfection assay has been accomplished. These results demonstrate that the new ammonium-terminated carbosilane dendrimers are good base molecules to be considered for biomedical applications.
authors.affiliation: Laboratorio de Inmunobiología Molecular, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Jesus F
authors.initials: JF
authors.lastname: Bermejo
authors.forename: Paula
authors.initials: P
authors.lastname: Ortega
authors.forename: Louis
authors.initials: L
authors.lastname: Chonco
authors.forename: Ramon
authors.initials: R
authors.lastname: Eritja
authors.forename: Rafael
authors.initials: R
authors.lastname: Samaniego
authors.forename: Matthias
authors.initials: M
authors.lastname: Müllner
authors.forename: Ernesto
authors.initials: E
authors.lastname: de Jesus
authors.forename: F Javier
authors.initials: FJ
authors.lastname: de la Mata
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Flores
authors.forename: Rafael
authors.initials: R
authors.lastname: Gomez
authors.forename: Angeles
authors.initials: A
authors.lastname: Muñoz-Fernandez
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D050091:Dendrimers / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D004587:Electrophoresis, Agar Gel; D004912:Erythrocytes / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D008856:Microscopy, Fluorescence; D015394:Molecular Structure; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D010957:Plasmids / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics; D015203:Reproducibility of Results; D012821:Silanes / Q000737:chemistry*; D012995:Solubility; D014162:Transfection / Q000379:methods; D014867:Water / Q000737:chemistry
chemical_list: D050091:Dendrimers; D009838:Oligodeoxyribonucleotides; D012821:Silanes; C504072:carbosilane; D014867:Water