title: Hyaluronic acid-conjugated lipoplexes for targeted delivery of siRNA in a murine metastatic lung cancer model.
abstract: We have investigated the impact of hyaluronic acid (HA)-coating on the targeting capacity of siRNA lipoplexes to CD44-overexpressing tumor cells. Cellular uptake and localization of HA-lipoplexes were evaluated by flow cytometry and fluorescence microscopy and both methods showed that these lipoplexes were rapidly internalized and localized primarily within the cytoplasm. Inhibition of luciferase expression on the A549-luciferase lung cancer cell line was achieved in vitro using an anti-Luc siRNA. 81% of luciferase gene expression inhibition was obtained in vitro with HA-lipoplexes at +/- ratio 2. In vivo, in a murine A549 metastatic lung cancer model, the treatment with HA-lipoplexes carrying anti-luciferase siRNA led to a statistically significant decrease of luciferase expression as opposed to progressive increase with non-modified lipoplexes or NaCl 0.9%. The reduction of the expression of luciferase mRNA tumor of mice treated with HA-lipoplexes supported the inhibition effect due to siRNA. These results highlight the potential of HA-lipoplexes in CD44-targeting siRNA delivery.
authors.affiliation: Université Paris-Sud, Faculté de Pharmacie, Institut Galien Paris-Sud, 5 rue JB Clément, 92296 Châtenay-Malabry Cedex, France; CNRS, UMR 8612, 5 rue JB Clément, 92296 Châtenay-Malabry Cedex, France; CAPES Foundation, Ministry of Education of Brazil, Brasília- DF 70040-020, Brazil.
authors.forename: Thais
authors.initials: T
authors.lastname: Leite Nascimento
authors.affiliation: Université Paris-Sud, Faculté de Pharmacie, Institut Galien Paris-Sud, 5 rue JB Clément, 92296 Châtenay-Malabry Cedex, France; CNRS, UMR 8612, 5 rue JB Clément, 92296 Châtenay-Malabry Cedex, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Hillaireau
authors.affiliation: Université Paris-Sud, Faculté de Pharmacie, Institut Galien Paris-Sud, 5 rue JB Clément, 92296 Châtenay-Malabry Cedex, France; CNRS, UMR 8612, 5 rue JB Clément, 92296 Châtenay-Malabry Cedex, France.
authors.forename: Juliette
authors.initials: J
authors.lastname: Vergnaud
authors.affiliation: Université Paris-Sud, Faculté de Pharmacie, Institut Galien Paris-Sud, 5 rue JB Clément, 92296 Châtenay-Malabry Cedex, France; CNRS, UMR 8612, 5 rue JB Clément, 92296 Châtenay-Malabry Cedex, France.
authors.forename: Melania
authors.initials: M
authors.lastname: Rivano
authors.affiliation: UMS-IPSIT-US 31 Inserm-UMS 3979 CNRS, 5 rue JB Clément, 92296 Châtenay-Malabry Cedex, France.
authors.forename: Claudine
authors.initials: C
authors.lastname: Deloménie
authors.affiliation: UMS-IPSIT-US 31 Inserm-UMS 3979 CNRS, 5 rue JB Clément, 92296 Châtenay-Malabry Cedex, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Courilleau
authors.affiliation: Università degli Studi di Torino, Facoltà di Farmacia, Dipartemento di Scienza e Tecnologia del Farmaco, Via Pietro Giuria 9, 10125 Torino, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Arpicco
authors.affiliation: Center for Nanomedicine, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231; USA, USA; Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21297; USA, USA; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218; USA, USA.
authors.forename: Jung Soo
authors.initials: JS
authors.lastname: Suk
authors.affiliation: Center for Nanomedicine, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231; USA, USA; Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21297; USA, USA; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218; USA, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Hanes
authors.affiliation: Université Paris-Sud, Faculté de Pharmacie, Institut Galien Paris-Sud, 5 rue JB Clément, 92296 Châtenay-Malabry Cedex, France; CNRS, UMR 8612, 5 rue JB Clément, 92296 Châtenay-Malabry Cedex, France. Electronic address: elias.fattal@u-psud.fr.
authors.forename: Elias
authors.initials: E
authors.lastname: Fattal
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D006820:Hyaluronic Acid / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D008156:Luciferases / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy*; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000737:chemistry*
chemical_list: D018960:Hyaluronan Receptors; D008081:Liposomes; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D006820:Hyaluronic Acid; D008156:Luciferases
keywords: A549; CD44; Hyaluronic acid; Lipoplexes; Luciferase; siRNA