Water‐Soluble Carbosilane Dendrimers: Synthesis Biocompatibility and Complexation with Oligonucleotides; Evaluation for Medical Applications
2007
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 SiCl bonds with amino alcohols and subsequent quaternization with MeI, and 2) hydrosilylation of allylamine with SiH 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 SiO bonds. However, dendrimers containing SiC 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.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
43
References
133
Citations
NaN
KQI