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Article

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

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Institute of Cellular Biology and Pathology "Nicolae Simionescu,” 050568 Bucharest, Romania
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University of Agronomic Sciences and Veterinary Medicine (UASVM), Faculty of Veterinary Medicine, 050097 Bucharest, Romania
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University of Agronomic Sciences and Veterinary Medicine (UASVM), Faculty of Biotechnologies, 011464 Bucharest, Romania
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Centre National de la Recherche Scientifique (CNRS), Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS) UMR 8258, 75006 Paris, France
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Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS) U 1022, 75006 Paris, France
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Université Paris Descartes, Sorbonne-Paris-Cité University, Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS), 75006 Paris, France
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Chimie ParisTech, PSL Research University, UTCBS, 75005 Paris, France
*
Author to whom correspondence should be addressed.
Pharmaceutics 2019, 11(1), 47; https://doi.org/10.3390/pharmaceutics11010047
Received: 20 December 2018 / Revised: 17 January 2019 / Accepted: 17 January 2019 / Published: 21 January 2019
(This article belongs to the Special Issue Non-Ionic Surfactant Vesicles for Drug Delivery)
: 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. View Full-Text
Keywords: endothelial cells; P-selectin; siRNA; targeted delivery; liposomes; gene silencing endothelial cells; P-selectin; siRNA; targeted delivery; liposomes; gene silencing
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MDPI and ACS Style

Constantinescu, C.A.; Fuior, E.V.; Rebleanu, D.; Deleanu, M.; Simion, V.; Voicu, G.; Escriou, V.; Manduteanu, I.; Simionescu, M.; Calin, M. Targeted Transfection Using PEGylated Cationic Liposomes Directed Towards P-Selectin Increases siRNA Delivery into Activated Endothelial Cells. Pharmaceutics 2019, 11, 47. https://doi.org/10.3390/pharmaceutics11010047

AMA Style

Constantinescu CA, Fuior EV, Rebleanu D, Deleanu M, Simion V, Voicu G, Escriou V, Manduteanu I, Simionescu M, Calin M. Targeted Transfection Using PEGylated Cationic Liposomes Directed Towards P-Selectin Increases siRNA Delivery into Activated Endothelial Cells. Pharmaceutics. 2019; 11(1):47. https://doi.org/10.3390/pharmaceutics11010047

Chicago/Turabian Style

Constantinescu, Cristina Ana, Elena Valeria Fuior, Daniela Rebleanu, Mariana Deleanu, Viorel Simion, Geanina Voicu, Virginie Escriou, Ileana Manduteanu, Maya Simionescu, and Manuela Calin. 2019. "Targeted Transfection Using PEGylated Cationic Liposomes Directed Towards P-Selectin Increases siRNA Delivery into Activated Endothelial Cells" Pharmaceutics 11, no. 1: 47. https://doi.org/10.3390/pharmaceutics11010047

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