Targeted Transfection Using PEGylated Cationic Liposomes Directed Towards P-Selectin Increases siRNA Delivery into Activated Endothelial Cells

Cristina Ana Constantinescu (1, 2) , Elena Valeria Fuior (1) , Daniela Rebleanu (1) , Mariana Deleanu (1) , Viorel Simion (1) , Geanina Voicu (1) , Virginie Escriou (3) , Ileana Manduteanu (1) , Maya Simionescu (1) , Manuela Calin (1)

1 Institute of Cellular Biology and Pathology Nicolae Simionescu [Bucarest, Romania]
2 UASVM - University of Agronomical Sciences and Veterinary Medicine
3 UTCBS - UM 4 (UMR 8258 / U1022) - Unité de Technologies Chimiques et Biologiques pour la Santé

The progress in small-interfering RNA (siRNA) therapeutics depends on the development of suitable nanocarriers to perform specific and effective delivery to dysfunctional cells. In this paper, we questioned whether P-selectin, a cell adhesion molecule specifically expressed on the surface of activated endothelial cells (EC) could be employed as a target for nanotherapeutic intervention. To this purpose, we developed and characterized P-selectin targeted PEGylated cationic liposomes able to efficiently pack siRNA and to function as efficient vectors for siRNA delivery to tumour necrosis factor-α (TNF-α) activated EC. Targeted cationic liposomes were obtained by coupling a peptide with high affinity for P-selectin to a functionalized PEGylated phospholipid inserted in the liposomes' bilayer (Psel-lipo). As control, scrambled peptide coupled cationic liposomes (Scr-lipo) were used. The lipoplexes obtained by complexation of Psel-lipo with siRNA (Psel-lipo/siRNA) were taken up specifically and at a higher extent by TNF-α activated b.End3 endothelial cells as compared to non-targeted Scr-lipo/siRNA. The Psel-lipo/siRNA delivered with high efficiency siRNA into the cells. The lipoplexes were functional as demonstrated by the down-regulation of the selected gene (GAPDH). The results demonstrate an effective targeted delivery of siRNA into cultured activated endothelial cells using P-selectin directed PEGylated cationic liposomes, which subsequently knock-down the desired gene.

Mots clés: targeted delivery; gene silencing; liposomes; endothelial cells; P-selectin; siRNA

Domaines: Sciences pharmaceutiques; Ingénierie biomédicale; Biotechnologies

Cristina Ana Constantinescu, Elena Valeria Fuior, Daniela Rebleanu, Mariana Deleanu, Viorel Simion, et al.. Targeted Transfection Using PEGylated Cationic Liposomes Directed Towards P-Selectin Increases siRNA Delivery into Activated Endothelial Cells. Pharmaceutics, 2019, 11 (1), pp.47. ⟨10.3390/pharmaceutics11010047⟩. ⟨hal-02360735⟩