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Nucleic Acids Research Advance Access published online on December 13, 2007
Nucleic Acids Research, doi:10.1093/nar/gkm1094
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© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Methods Online

siRNA nanoformulation against the Ret/PTC1 junction oncogene is efficient in an in vivo model of papillary thyroid carcinoma

Henri de Martimprey1,2,*, Jean-Remi Bertrand1, Alfredo Fusco3, Massimo Santoro3, Patrick Couvreur2, Christine Vauthier2 and Claude Malvy1

1CNRS, UMR 8121, Univ Paris-Sud, Institut Gustave Roussy, 2CNRS, UMR 8612, Univ Paris-Sud, Faculté de Pharmacie and 3Istituto di Endocrinologia ed Oncologia Sperimentale del CNR "G.Salvatore", c/o Dipartimento di Biologia e Patologia Cellulare e Molecolare, Universita’ Federico II, Naples, Italy

*To whom correspondence should be addressed. Tel: +33 142 115062; Fax: +33 142 115245; Email: martimprey{at}igr.fr

Received July 27, 2007. Revised October 17, 2007. Accepted November 23, 2007.

Delivery is a very important concern for therapeutic applications of siRNA. In this study, we have used chitosan-coated poly(isobutylcyanoacrylate) nanoparticles to deliver siRNA with a complementary sequence to the fusion oncogene ret/PTC1. By screening the mRNA junction we have selected a potent siRNA sequence able to inhibit this oncogene in a model of Papillary Thyroid Carcinoma cells. This siRNA sequence has then been validated by a shRNA approach using the same sequence. Furthermore, the high ret/PTC1 inhibition has triggered a phenotypic reversion of the transformed cells. We have designed well-defined chitosan decorated nanoparticles and succeeded to reduce their size. They have allowed to protect ret/PTC1 siRNA from in vivo degradation and leading to significant tumour growth inhibition after intratumoral administration.


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