In Vitro Studies of Water-Stable Cationic Carbosilane Dendrimers As Delivery Vehicles for Gene Therapy Against HIV and Hepatocarcinoma

Author(s): N. de las Cuevas, S. Garcia-Gallego, B. Rasines, F.J. de la Mata, L. G. Guijarro, M.A. Munoz-Fernandez, R. Gomez.

Journal Name: Current Medicinal Chemistry

Volume 19 , Issue 29 , 2012

Abstract:

Here we present a synthetic procedure for water-stable carbosilane dendrimers containing ammonium groups at the periphery of type Gn-{[Si(CH2)3N+(Me)(Et)CH2CH2N+Me3]x (CF3SO3 -)y} which have been used as non-viral vectors for transfecting different types of nucleic acids against two different medical problems, HIV and hepatocarcinoma. These systems have shown to be non-toxic in both PBMC and HepG2 cell lines under the experimental conditions and are able to form nanoconjugates with nucleic acids perfectly stable over time and in a wide range of pH values, which leads to the conclusion that the interaction between dendrimer and nucleic acid is very strong. In addition, a high degree of transfection using these nanoconjugates has been observed, ranging from 70-90% depending on the generation and in the particular case of PBMC transfection with anti-HIV oligonucleotides. However, besides of the good properties shown by the dendrimers here prepared as transfecting agents, only moderate effect was observed in functional experiments for hepatocarcinoma, as a result of the strong interaction between dendrimer and nucleic acid. Nevertheless, it is important to mention that an IRS-4 knock-down of 40% in HepG2 achieves an analogous degree of cell sensitization to cancer treatment, which may represent a major advance in the hepatocarcinoma treatment when appropriate dendrimers as transfection agents are used.

Keywords: Dendrimer, carbosilane, oligonucleotides, siRNA, drug delivery, gene therapy, transfection agent, HIV, cancer

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Article Details

VOLUME: 19
ISSUE: 29
Year: 2012
Page: [5052 - 5061]
Pages: 10
DOI: 10.2174/0929867311209025052
Price: $58

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