Water-soluble carbosilane dendrimers:: Synthesis biocompatibility and complexation with oligonucleotides;: Evaluation for medical applications

Novel amine- or ammonium-terminated carbosilane dendrimers of type nG-[Si{OCH2(C6H3)-3,5-(OCH2-CH2NMe2)(2)}](x), nG-[Si{O(CH2)(2)N(Me)(CH2)(2)NMe2}](x) and nG-[Si{(CH2)(3)-NH2}](x) or nG-[Si{OCH2(C6H3)-3,5(OCH2CH2NMe3+I-)(2)}](x), nG-[Si{O(CH2)(2)N(Me)(CH2)(2)NMe3+I-}](x) and nG-[Si{(CH2)(3)NH2+Cl-}], 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 HCI. 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 oligodeoxy-nucleotides (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.