title: Delivery of siRNA into the cytoplasm by liposomal bubbles and ultrasound.
abstract: Small interfering RNA (siRNA) is expected to be a novel therapeutic tool, however, its utilization has been limited by inefficient delivery systems. Recently, we have developed novel polyethyleneglycol modified liposomes (Bubble liposomes; BL) entrapping an ultrasound (US) imaging gas, which can work as a gene delivery tool with US exposure. In this study, we investigated whether the BL were suitable for the delivery of siRNA. BL efficiently delivered siRNA with only 10 s of exposure to US in vitro. Specific gene silencing effects could be achieved well even in the presence of serum or with the disruption of endocytosis. We suggest that siRNA is directly introduced into the cytoplasm by the BL and US and the mechanism enables effective transfection within a short time and in the presence of high serum. Transfection of siRNA into the tibialis muscles with BL and US was also performed. The gene-silencing effect could be sustained for more than 3 weeks. Thus, BL could be a useful siRNA delivery tool in vitro and in vivo.
authors.affiliation: Department of Drug and Gene Delivery System, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan. negishi@ps.toyaku.ac.jp
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Negishi
authors.forename: Yoko
authors.initials: Y
authors.lastname: Endo
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Fukuyama
authors.forename: Ryo
authors.initials: R
authors.lastname: Suzuki
authors.forename: Tomoko
authors.initials: T
authors.lastname: Takizawa
authors.forename: Daiki
authors.initials: D
authors.lastname: Omata
authors.forename: Kazuo
authors.initials: K
authors.lastname: Maruyama
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Aramaki
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D002738:Chloroquine / Q000494:pharmacology; D003593:Cytoplasm / Q000378:metabolism; D005466:Fluorocarbons / Q000737:chemistry; D015870:Gene Expression / Q000187:drug effects; D018014:Gene Transfer Techniques; D007668:Kidney / Q000378:metabolism; D008055:Lipids / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry*; D049409:Luciferases, Firefly / Q000235:genetics / Q000378:metabolism; D051379:Mice; D045423:Microbubbles; D018482:Muscle, Skeletal / Q000378:metabolism; D041681:NIH 3T3 Cells; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics; D044967:Serum / Q000737:chemistry; D012867:Skin / Q000378:metabolism; D014162:Transfection; D014465:Ultrasonics
chemical_list: D005466:Fluorocarbons; D008055:Lipids; C086724:Lipofectamine; D008081:Liposomes; D010714:Phosphatidylethanolamines; D034741:RNA, Small Interfering; C038089:1,2-distearoylphosphatidylethanolamine; D015060:1,2-Dipalmitoylphosphatidylcholine; D011092:Polyethylene Glycols; D002738:Chloroquine; C042852:perflutren; D049409:Luciferases, Firefly