[en] The use of small interfering RNA (siRNA) to regulate oncogenes appears as a promising strategy in the context of cancer therapy, especially if they are vectorized by a smart delivery system. In this study, we investigated the cellular trafficking of a siRNA nanovector (called CS-MSN) functionalized with the cell-penetrating peptide gH625 in a triple-negative breast cancer model. With complementary techniques, we showed that siRNA nanovectors were internalized by both clathrin- and caveolae-mediated endocytosis. The presence of gH625 at the surface of the siRNA nanovector did not modify the entry pathway of CS-MSN, but it increased the amount of siRNA found inside the cells. Results suggested an escape of siRNA from endosomes, which is enhanced by the presence of the peptide gH625, whereas nanoparticles continued their trafficking into lysosomes. The efficiency of CS-MSN to inhibit the GFP in MDA-MB-231 cells was 1.7-fold higher than that of the nanovectors without gH625.
Disciplines :
Oncology
Author, co-author :
Ben Djemaa, Sanaa ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques ; EA6295 Nanomédicaments et Nanosondes, University of Tours , 37200 Tours , France
Hervé-Aubert, Katel ; EA6295 Nanomédicaments et Nanosondes, University of Tours , 37200 Tours , France
Lajoie, Laurie; EA7501 Groupe Innovation et Ciblage Cellulaire, Equipe Fc Récepteurs, Anticorps et MicroEnvironnement, University of Tours , 37032 Tours , France ; Plateforme Scientifique et Technique, Analyse des systèmes biologiques département des cytométries, University of Tours , 37032 Tours , France
Falanga, Annarita; Department of Agricultural Sciences , University of Naples "Federico II" , Via Università 100 , 80055 Portici , Italy
Galdiero, Stefania; Department of Pharmacy , CIRPEB-University of Naples "Federico II" , Via Mezzocannone 16 , 80134 Napoli , Italy
Nedellec, Steven; Plateforme microPICell, SFR santé François Bonamy-IRSUN , 8 quai Moncousu , BP 70721, 44007 Nantes Cedex, France
Soucé, Martin ; EA6295 Nanomédicaments et Nanosondes, University of Tours , 37200 Tours , France
Munnier, Emilie; EA6295 Nanomédicaments et Nanosondes, University of Tours , 37200 Tours , France
Chourpa, Igor; EA6295 Nanomédicaments et Nanosondes, University of Tours , 37200 Tours , France
David, Stéphanie; EA6295 Nanomédicaments et Nanosondes, University of Tours , 37200 Tours , France
Allard-Vannier, Emilie ; EA6295 Nanomédicaments et Nanosondes, University of Tours , 37200 Tours , France
Language :
English
Title :
gH625 Cell-Penetrating Peptide Promotes the Endosomal Escape of Nanovectorized siRNA in a Triple-Negative Breast Cancer Cell Line.
CAMPUS France LNCC - Ligue Nationale Contre le Cancer Cancéropôle du Grand Ouest Region Centre-Val de Loire
Funding text :
We are grateful to the “Ligue Nationale Contre le Cancer” for their financial support and especially to the local committees of the departments 17, 37, 49, 53, and 56 (EVASION project and INTERACTION project). We also thank the “Région Centre-Val de Loire”, the “Cancéropole Grand Ouest” (MATURE project), and Campus France (PHC GALILEE 2017, project No 39635TB) for the funding.
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