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Formulation and in vitro evaluation of a siRNA delivery nanosystem decorated with gH625 peptide for triple negative breast cancer theranosis.

Research paper by Sanaa S Ben Djemaa, Stephanie S David, Katel K Hervé-Aubert, Annarita A Falanga, Stefania S Galdiero, Emilie E Allard-Vannier, Igor I Chourpa, Emilie E Munnier

Indexed on: 01 Aug '18Published on: 01 Aug '18Published in: European Journal of Pharmaceutics and Biopharmaceutics



Abstract

The development of an efficient small interfering RNA (siRNA) delivery system has held scientists interest since the discovery of the RNA interference mechanism (RNAi). This strategy gives hope for the treatment of many severe diseases. Herein, we developed hybrid nanovectors able to deliver siRNA to triple negative breast cancer cells. The nanovectors are based on PEGylated superparamagnetic iron oxide nanoparticles (SPION) functionalized with gH625 peptide, chitosan and poly-L-arginine. Every component has a key role and specific function: SPION is the core scaffolding the nanovector; PEG participates in the colloidal stability and the immune stealthiness; gH625 peptide promotes the nanovector internalization into cancer cells; cationic polymers provide the siRNA protection and favor siRNA endosomal escape and delivery to cytosol. The formulation was optimized by varying the amount of each compound. The efficacy of the siRNA retention and protection were investigated in the presence of high concentration of serum. Optimized nanovectors show a high uptake by MDA-MB-231 cells. The resulting down regulation of GFP expression was 73 +/- 3% with our nanovector compared to 59 +/- 8% obtained with the siRNA-Oligofectamine™ complex in the same conditions. Copyright © 2018. Published by Elsevier B.V.