title: SAINT-liposome-polycation particles, a new carrier for improved delivery of siRNAs to inflamed endothelial cells.
abstract: Interference with acute and chronic inflammatory processes by means of delivery of siRNAs into microvascular endothelial cells at a site of inflammation demands specific, non-toxic and effective siRNA delivery system. In the current work we describe the design and characterization of siRNA carriers based on cationic pyridinium-derived lipid 1-methyl-4-(cis-9-dioleyl)methyl-pyridinium-chloride) (SAINT-C18) and the transfection enhancer protamine, complexed with siRNA/carrier DNA or siRNA only. These carriers, called SAINT-liposome-polycation-DNA (S-LPD) and SAINT-liposome-polycation (S-LP), have a high efficiency of siRNA encapsulation, low cellular toxicity, and superior efficacy of gene downregulation in endothelial cells in vitro as compared to DOTAP-LPD. Incorporation of 10 mol% PEG and anti-E-selectin antibody in these formulations resulted in selective siRNA delivery into activated endothelial cells. Furthermore, we showed that the physicochemical characteristics of S-LPD and S-LP, including size-stability and maintenance of the siRNA integrity in the presence of serum at 37 °C, comply with requirements for in vivo application.
authors.affiliation: University of Groningen, University Medical Center Groningen, Dept. of Pathology & Medical Biology, Medical Biology Section, Groningen, The Netherlands.
authors.forename: Piotr S
authors.initials: PS
authors.lastname: Kowalski
authors.affiliation: University of Groningen, University Medical Center Groningen, Dept. of Pathology & Medical Biology, Medical Biology Section, Groningen, The Netherlands.
authors.forename: Praneeth R
authors.initials: PR
authors.lastname: Kuninty
authors.affiliation: University of Groningen, University Medical Center Groningen, Dept. of Pathology & Medical Biology, Medical Biology Section, Groningen, The Netherlands.
authors.forename: Klaas T
authors.initials: KT
authors.lastname: Bijlsma
authors.affiliation: University of Groningen, Groningen Biomolecular Sciences and Biotechnology Institute, The Netherlands; Stratingh Institute, University of Groningen, Groningen, The Netherlands.
authors.forename: Marc C A
authors.initials: MC
authors.lastname: Stuart
authors.affiliation: University of Groningen, University Medical Center Groningen, Dept. of Pathology & Medical Biology, Medical Biology Section, Groningen, The Netherlands.
authors.forename: Niek G J
authors.initials: NG
authors.lastname: Leus
authors.affiliation: University of Groningen, University Medical Center Groningen, Dept. of Pathology & Medical Biology, Medical Biology Section, Groningen, The Netherlands; Synvolux Therapeutics, Groningen, The Netherlands.
authors.forename: Marcel H J
authors.initials: MH
authors.lastname: Ruiters
authors.affiliation: University of Groningen, University Medical Center Groningen, Dept. of Pathology & Medical Biology, Medical Biology Section, Groningen, The Netherlands.
authors.forename: Grietje
authors.initials: G
authors.lastname: Molema
authors.affiliation: University of Groningen, University Medical Center Groningen, Dept. of Pathology & Medical Biology, Medical Biology Section, Groningen, The Netherlands. Electronic address: j.a.a.m.kamps@umcg.nl.
authors.forename: Jan A A M
authors.initials: JA
authors.lastname: Kamps
mesh_terms: D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004247:DNA / Q000494:pharmacology; D004337:Drug Carriers / Q000494:pharmacology*; D016503:Drug Delivery Systems / Q000379:methods; D019040:E-Selectin / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D008055:Lipids / Q000494:pharmacology; D008081:Liposomes / Q000494:pharmacology*; D010316:Particle Size; D011073:Polyamines / Q000494:pharmacology*; D000071228:Polyelectrolytes; D011726:Pyridinium Compounds / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000494:pharmacology*; D014162:Transfection / Q000379:methods
chemical_list: D004247:DNA; D004337:Drug Carriers; D019040:E-Selectin; D008055:Lipids; D008081:Liposomes; D011073:Polyamines; D000071228:Polyelectrolytes; D011726:Pyridinium Compounds; D034741:RNA, Small Interfering; C532953:1-methyl-4-(9-dioleyl)methylpyridinium
keywords: Cationic lipid; E-selectin; Endothelium; Inflammation; Liposome-polycation-DNA; Targeted siRNA delivery