[en] 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.
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Ben Djemaa, Sanaa ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques ; EA6295 Nanomédicaments et Nanosondes, Université de Tours, 31 Avenue Monge, 37200 Tours, France
David, Stephanie ; EA6295 Nanomédicaments et Nanosondes, Université de Tours, 31 Avenue Monge, 37200 Tours, France. Electronic address: stephanie.david@univ-tours.fr
Hervé-Aubert, Katel; EA6295 Nanomédicaments et Nanosondes, Université de Tours, 31 Avenue Monge, 37200 Tours, France
Falanga, Annarita ; Department of Pharmacy, CIRPEB - University of Naples "Federico II", Via Mezzocannone 16, 80134 Napoli, Italy
Galdiero, Stefania; Department of Pharmacy, CIRPEB - University of Naples "Federico II", Via Mezzocannone 16, 80134 Napoli, Italy
Allard-Vannier, Emilie ; EA6295 Nanomédicaments et Nanosondes, Université de Tours, 31 Avenue Monge, 37200 Tours, France
Chourpa, Igor; EA6295 Nanomédicaments et Nanosondes, Université de Tours, 31 Avenue Monge, 37200 Tours, France
Munnier, Emilie; EA6295 Nanomédicaments et Nanosondes, Université de Tours, 31 Avenue Monge, 37200 Tours, France
Language :
English
Title :
Formulation and in vitro evaluation of a siRNA delivery nanosystem decorated with gH625 peptide for triple negative breast cancer theranosis.
Publication date :
October 2018
Journal title :
European Journal of Pharmaceutics and Biopharmaceutics
Region Centre-Val de Loire Cancéropôle du Grand Ouest
Funding text :
This work was funded by the “Région Centre-Val de Loire” (MATURE Project) and supported by the “Cancéropôle Grand Ouest”. We thank Isabelle Dimier-Poisson, Nathalie Moire and Zineb Lakhrif (UMR INRA 1282, team of “Infectiologie et Santé Publique” University of Tours) for their help with flow cytometry experiments.This work was funded by the “ Région Centre-Val de Loire ” (MATURE Project) and supported by the “ Cancéropôle Grand Ouest ”. We thank Isabelle Dimier-Poisson, Nathalie Moire and Zineb Lakhrif (UMR INRA 1282, team of “Infectiologie et Santé Publique”, University of Tours) for their help with flow cytometry experiments.
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