Journal
MOLECULAR PHARMACEUTICS
Volume 9, Issue 3, Pages 433-447Publisher
AMER CHEMICAL SOC
DOI: 10.1021/mp200542j
Keywords
dendrimer; carbosilane; cationic; click chemistry; gene therapy; cancer
Funding
- Fondo de Investigacion Sanitaria [PI080222]
- Proyecto CAM-UAH [CCG10-UAH/PPQ-5916]
- University of Navarra Foundation
- Caja de Ahorros de Navarra (CAN)
- Consejeria de Educacion de la Comunidad de Madrid
- Fondo Social Europe
- VI National RDi Plan
- Iniciativa Ingenio
- Consolider Program
- CIBER Actions
- Instituto de Salud Carlos III
- European Regional Development Fund
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New amine-terminated carbosilane dendrimers have been prepared by a Huisgen cycloaddition (click chemistry 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 (+/-)) 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 (+/-) is superior in terms of gene transfer efficiency in vivo.
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