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Article Dans Une Revue Oligonucleotides. Année : 2006

Antisense oligonucleotide nanocapsules efficiently inhibit EWS-Fli1 expression in a Ewing's sarcoma model.

Résumé

The cytogenetic abnormality of Ewing's sarcoma is related to the presence of a balanced t(11;22) translocation expressing the EWS-Fli1 chimeric fusion protein. Oligonucleotides (ODNs) are specific compounds that inhibit gene expression at the transcriptional level. They possess a poor bioavailability and are degraded by nucleases very rapidly. Therefore, there is a strong need for the development of ODN drug delivery systems. In the present study, polyisobutylcyanoacrylate nanocapsules entrapping ODNs in their aqueous core were prepared, with high encapsulation yield (99%). Previous studies have demonstrated that such complexes were able to inhibit tumor growth in mice. Nevertheless, no information was available about their mode of action at the cellular level. The aim of this study was to investigate the efficacy of these ODN nanocapsules on cultured tumor cells. We found that nanocapsules were capable of protecting ODN against degradation. Using confocal microscopy, we observed that cell uptake and nuclear accumulation of ODNs were importantly enhanced when ODNs were associated with these nanocapsules. Consequently, a specific cellular growth inhibition and suppression of EWSFli1 fusion gene expression was noticed. In conclusion, it was demonstrated that nanocapsules as nonviral vectors show great potential for the delivery of ODNs to cells.
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Dates et versions

hal-00091082 , version 1 (05-09-2006)

Identifiants

  • HAL Id : hal-00091082 , version 1

Citer

Toub Nedjma, Jean-Rémi Bertrand, Claude Malvy, Elias Fattal, Patrick Couvreur. Antisense oligonucleotide nanocapsules efficiently inhibit EWS-Fli1 expression in a Ewing's sarcoma model.. Oligonucleotides., 2006, 16, pp.158-168. ⟨hal-00091082⟩
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