Synthesis of Cationic Carbosilane Dendrimers via Click Chemistry and Their Use as Effective Carriers for DNA Transfection into Cancerous Cells
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- 作者：Eduardo Arn谩iz ; Lorena I. Doucede ; Sandra Garc铆a-Gallego ; Koldo Urbiola ; Rafael G贸mez ; Conchita Tros de Ilarduya ; F. Javier de la Mata
- 刊名：Molecular Pharmaceutics
- 出版年：2012
- 出版时间：March 5, 2012
- 年：2012
- 卷：9
- 期：3
- 页码：433-447
- 全文大小：519K
- 年卷期：v.9,no.3(March 5, 2012)
- ISSN：1543-8392
文摘
New amine-terminated carbosilane dendrimers have been prepared by a Huisgen cycloaddition (鈥渃lick chemistry鈥?reaction) of azide-terminated carbosilane dendrimers with two different propargyl amines. The corresponding cationic derivatives with peripheral ammonium groups were obtained by subsequent addition of MeI. Quaternized dendrimers are soluble and stable in water or other protic solvents for long time periods, and have been studied as nonviral vectors for the transfection of DNA to cancer cells. In this study DNA-dendrimeric nanoparticles (dendriplexes) formulated with two different families of cationic carbosilane dendrimers (family 1 (G1, G2 and G3) and family 2 (G1, G2)) were characterized and evaluated for their ability to transfect cells in vitro and in vivo. Dendriplex derived from second generation dendrimer of family 1 (F1G2 5/1 (+/鈭?) increased the efficiency of plasmid-mediated gene transfer in HepG2 cells as compared to naked DNA and the commercial control dendrimer. Also, intravenously administered dendriplex F1G3 20/1 (+/鈭? is superior in terms of gene transfer efficiency in vivo.