[en] The endogenous mechanism of RNA interference is more and more used in research to obtain specific down-regulation of gene expression in diseases such as breast cancer. Currently, despite the new fields of study open up by RNA interference, the rapid degradation of siRNA by nucleases and their negative charges prevent them from crossing cell membranes. To overcome these limitations, superparamagnetic iron oxide nanoparticles (SPIONs) represent a promising alternative for nucleic acid delivery. Previously, we reported the magnetic siRNA nanovectors (MSN) formulation using electrostatic assembly of (1) SPIONs, also able to act as contrast agents for magnetic resonance imaging (MRI), (2) siRNA and (3) chitosan aiming at their protection and enhancing their transfection efficacy. However, these nanoparticles displayed low stability in biological suspensions and inefficient transfection of active siRNA. This work aimed at upgrading MSN to Stealth MSN (S-MSN) by adding a polyethylene glycol coating to ensure colloidal stability and stealth properties. Furthermore, another polymer (poly-L-arginine) was added for efficient siRNA transfection and the quantitative composition of the formulation was adapted for biological purposes. Results showed that S-MSN provide high siRNA complexation and protection against enzymatic degradation. Green fluorescent protein (GFP) specific down-regulation on MDA-MB231/GFP cells was comparable to that of commercially available reagents, without observable cytotoxicity. According to our works, S-MSN appears as an effective formulation for in vitro siRNA specific delivery.
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Bruniaux, J; Université François-Rabelais, EA6295 « Nanomédicaments et Nanosondes », Tours, 37200, France
Ben Djemaa, Sanaa ; Université de Liège - ULiège > GIGA > GIGA Molecular Biology of Diseases - Gene Expression & Cancer
Hervé-Aubert, K; Université François-Rabelais, EA6295 « Nanomédicaments et Nanosondes », Tours, 37200, France
Marchais, H; Université François-Rabelais, EA6295 « Nanomédicaments et Nanosondes », Tours, 37200, France
Chourpa, I; Université François-Rabelais, EA6295 « Nanomédicaments et Nanosondes », Tours, 37200, France
David, S; Université François-Rabelais, EA6295 « Nanomédicaments et Nanosondes », Tours, 37200, France. Electronic address: stephanie.david@univ-tours.fr
Language :
English
Title :
Stealth magnetic nanocarriers of siRNA as platform for breast cancer theranostics.
INCa - Institut National du Cancer [FR] Fondation ARC pour la Recherche sur le Cancer [FR] LNCC - Ligue Nationale Contre le Cancer [FR] Region Centre-Val de Loire [FR]
Funding text :
This work is supported by the “ Institut National du Cancer (INCa) ”, the “ Fondation ARC ” and the “ Ligue Nationale Contre le Cancer (LNCC) ” ( ARC_INCa_LNCC_7636 ). We are thankful to the " Région Centre-Val de Loire " (NCIS Project). The authors would like to thank Isabelle Dimier-Poisson and Nathalie Moire (UMR INRA 1282, team of “Infectiologie et Santé Publique”, University François Rabelais of Tours) for her help with flow cytometry experiments and Didier Bedin (EA6295, "Nanomédicaments et nanosondes", University François Rabelais of Tours) for technical support. Appendix AThis work is supported by the ?Institut National du Cancer (INCa)?, the ?Fondation ARC? and the ?Ligue Nationale Contre le Cancer (LNCC)? (ARC_INCa_LNCC_7636). We are thankful to the ?R?gion Centre-Val de Loire? (NCIS Project). The authors would like to thank Isabelle Dimier-Poisson and Nathalie Moire (UMR INRA 1282, team of ?Infectiologie et Sant? Publique?, University Fran?ois Rabelais of Tours) for her help with flow cytometry experiments and Didier Bedin (EA6295, ?Nanom?dicaments et nanosondes?, University Fran?ois Rabelais of Tours) for technical support.
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