Water-soluble carbosilane dendrimers: synthesis biocompatibility and complexation with oligonucleotides; evaluation for medical applications

[EN] 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 synth...

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Detalles Bibliográficos
Autores: Bermejo Martín, Jesús Francisco, Ortega, Paula, Chonco, Louis, Eritja, Ramon, Samaniego, Rafael, Müllner, Matthias, de Jesus, Ernesto, de la Mata, F Javier, Flores, Juan Carlos, Gomez, Rafael, Muñoz-Fernandez, Angeles
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2007
País:España
Institución:Universidad de Salamanca (USAL)
Repositorio:GREDOS. Repositorio Institucional de la Universidad de Salamanca
OAI Identifier:oai:gredos.usal.es:10366/161069
Acceso en línea:http://hdl.handle.net/10366/161069
Access Level:acceso embargado
Palabra clave:Cell Survival
Dendrimers
Electrophoresis, Agar Gel
Erythrocytes
Hemolysis
Leukocytes, Mononuclear
Molecular Structure
Transfection
Oligodeoxyribonucleotides
Humans
Plasmids
Leukocytes
Microscopy
Electrophoresis
Lymphocyte Activation
Silanes
Water
Solubility
Drug Delivery Systems
Reproducibility of Results
plásmidos
humanos
activación de linfocitos
transfección
estructura molecular
agua
microscopía
leucocitos
sistemas de liberación de medicamentos
reproducibilidad de resultados
solubilidad
dendrímeros
hemólisis
oligodesoxirribonucleótidos
silanos
eritrocitos
electroforesis
supervivencia celular
Descripción
Sumario:[EN] 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.

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