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Article Dans Une Revue International Journal of Pharmaceutics Année : 2021

Supramolecular organization and biological interaction of the squalenoyl siRNA nanoparticles

Résumé

Small interfering RNAs (siRNA) are attractive and powerful tools to inhibit the expression of a targeted gene. However, their extreme hydrophilicities combined with a negative charge and short plasma half-life counteract their use as therapeutics. Previously, we chemically linked siRNA to squalene (SQ) which self-assembled as nanoparticles (NPs) with pharmacological efficiency in cancers and recently in a hereditary neuropathy. In order to understand the siRNA-SQ NP assembly and fate once intravenously injected, the present study detailed characterization of siRNA-SQ NP structure and its interaction with serum components. From SAXS and SANS analysis, we propose that the siRNA-SQ bioconjugate self-assembled as 11-nm diameter supramolecular assemblies, which are connected one to another to form spherical nanoparticles of around 130-nm diameter. The siRNA-SQ NPs were stable in biological media and interacted with serum components, notably with albumin and LDL. The high specificity of siRNA to decrease or normalize gene expression and the high colloidal stability when encapsulated into squalene nanoparticles offer promising targeted therapy with wide applications for pathologies with gene expression dysregulation.

Domaines

Biologie animale
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Dates et versions

hal-03379142 , version 1 (14-10-2021)

Identifiants

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Marie Caillaud, Frédéric Gobeaux, Miryana Hémadi, Suzan Boutary, Patrick Guenoun, et al.. Supramolecular organization and biological interaction of the squalenoyl siRNA nanoparticles. International Journal of Pharmaceutics, 2021, 609, pp.121117. ⟨10.1016/j.ijpharm.2021.121117⟩. ⟨hal-03379142⟩
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