In Vitro Studies of Water-Stable Cationic Carbosilane Dendrimers As Delivery Vehicles for Gene Therapy Against HIV and Hepatocarcinoma
2012
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.
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