Synthesis, characterization, and in vivo delivery of siRNA-squalene nanoparticles targeting fusion oncogene in papillary thyroid carcinoma.

Abstract

We report the conjugation of the natural lipid squalene (SQ) with a small interfering RNA (siRNA), against the junction oncogene RET/PTC1, usually found in papillary thyroid carcinoma (PTC). The acyclic isoprenoid chain of squalene has been covalently coupled with siRNA RET/PTC1 at the 3'-terminus of the sense strand via maleimide-sulfhydryl chemistry. Remarkably, the linkage of siRNA RET/PTC1 to squalene led to an amphiphilic molecule that self-organized in H(2)O as siRNA-SQ RET/PTC1 nanoparticles (NPs). The siRNA-SQ RET/PTC1 NPs, stable in H(2)O, were used for biological studies. In vitro, they did not show any cytotoxicity. Interestingly, in vivo, on a mice xenografted RET/PTC1 experimental model, RET/PTC1-SQ NPs were found to inhibit tumor growth and RET/PTC1 oncogene and oncoprotein expression after 2.5 mg/kg cumulative dose intravenous injections. In conclusion, these results showed that the "squalenoylation" offers a new noncationic plate-form for the siRNA delivery.

DOI: 10.1021/jm2000272

Cite this paper

@article{Raouane2011SynthesisCA, title={Synthesis, characterization, and in vivo delivery of siRNA-squalene nanoparticles targeting fusion oncogene in papillary thyroid carcinoma.}, author={Mouna Raouane and Didier Desmaele and Marie Gilbert-Sirieix and Claire Gueutin and Fatima Zouhiri and Claudie Bourgaux and Elise Anne Lepeltier and Ruxandra Gref and Ridha Ben Salah and Gary L Clayman and Liliane Massaad-Massade and Patrick Couvreur}, journal={Journal of medicinal chemistry}, year={2011}, volume={54 12}, pages={4067-76} }