Small interfering RNA (siRNA); Superparamagnetic iron oxide nanoparticles (SPION); Survivin; scFv anti-HER2
Abstract :
[en] The association between superparamagnetic iron oxide nanoparticles (SPION), carrying small interfering RNA (siRNA) as therapeutic agents and humanized anti- human epidermal growth factor receptor-2 (HER2) single-chain antibody fragments (scFv) for the active delivery into HER2-overexpressing cells appears as an interesting approach for patients with HER2-overexpressing advanced breast cancer. The obtained Targeted Stealth Magnetic siRNA Nanovectors (TS-MSN) are formulated by combining: (i) the synthesis protocol of Targeted Stealth Fluorescent Particles (T-SFP) which form the core of TS-MSN and (ii) the formulation protocol allowing the loading of T-SFP with polyplexes (siRNA and cationic polymers). TS-MSN have suitable physico-chemical characteristics for intravenous administration and protect siRNA against enzymatic degradation up to 24 h. The presence of HER2-targeting scFv on TS-MSN allowed an improved internalization (3-4 times more compared to untargeted S-MSN) in HER2-overexpressing breast cancer cells (BT-474). Furthermore, anti-survivin siRNA delivered by TS-MSN in HER2-negative breast-cancer control cells (MDA-MB-231) allowed significant down-regulation of the targeted anti-apoptotic protein of about 70%. This protein down-regulation increased in HER2+ cells to about 90% (compared to 70% with S-MSN in both cell lines) indicating the contribution of the HER2-active targeting. In conclusion, TS-MSN are promising nanocarriers for the specific and efficient delivery of siRNA to HER2-overexpressing breast cancer cells.
Disciplines :
Human health sciences: Multidisciplinary, general & others
Author, co-author :
Bruniaux, J; Université de Tours, EA6295 «Nanomédicaments et Nanosondes», Tours 37200, France
Allard-Vannier, E; Université de Tours, EA6295 «Nanomédicaments et Nanosondes», Tours 37200, France
Aubrey, N; Université de Tours, UMR1282, INRA, «Infectiologie et Santé Publique», équipe BIOMAP, Tours 37200, France
Lakhrif, Z; Université de Tours, UMR1282, INRA, «Infectiologie et Santé Publique», équipe BIOMAP, Tours 37200, France
Ben Djemaa, Sanaa ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques ; Université de Tours, EA6295 «Nanomédicaments et Nanosondes», Tours 37200, France
Eljack, S; Université de Tours, EA6295 «Nanomédicaments et Nanosondes», Tours 37200, France
Marchais, H; Université de Tours, EA6295 «Nanomédicaments et Nanosondes», Tours 37200, France
Hervé-Aubert, K; Université de Tours, EA6295 «Nanomédicaments et Nanosondes», Tours 37200, France
Chourpa, I; Université de Tours, EA6295 «Nanomédicaments et Nanosondes», Tours 37200, France
David, S; Université de Tours, EA6295 «Nanomédicaments et Nanosondes», Tours 37200, France. Electronic address: stephanie.david@univ-tours.fr
Language :
English
Title :
Magnetic nanocarriers for the specific delivery of siRNA: Contribution of breast cancer cells active targeting for down-regulation efficiency.
This work was supported by the “Institut National du Cancer ( INCa )”, the “Fondation ARC” and the “Ligue Nationale Contre le Cancer (LNCC)” (ARC_INCa_LNCC_7636), France, the “Région Centre-Val de Loire” ( NCIS Project) and the “Cancéropole Grand Ouest” , France. “This work has been funded with support from the French Higher Education and Research ministry under the program “Investissements d’avenir” Grant Agreement: LabEx MAbImprove ANR-10-LABX-53–01.”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 their help with flow cytometry experiments and Lizzy Angevin for skillful technical support with cells.This work was supported by the ?Institut National du Cancer (INCa)?, the ?Fondation ARC? and the ?Ligue Nationale Contre le Cancer (LNCC)? (ARC_INCa_LNCC_7636), France, the ?R?gion Centre-Val de Loire? (NCIS Project) and the ?Canc?ropole Grand Ouest?, France. ?This work has been funded with support from the French Higher Education and Research ministry under the program ?Investissements d'avenir? Grant Agreement: LabEx MAbImprove ANR-10-LABX-53?01.?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 their help with flow cytometry experiments and Lizzy Angevin for skillful technical support with cells.
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