title: Development of anionic bubble lipopolyplexes for efficient and safe gene transfection with ultrasound exposure in mice.
abstract: Anionic bubble lipopolyplexes have been developed as anionic ultrasound (US)-responsive gene delivery carriers with biocompatible compounds for efficient and safe transfection in mice. The particles of the anionic bubble lipopolyplexes were approximately 450-600nm with an anionic surface charge. In the absence of US exposure, the bubble lipopolyplexes showed extremely low gene expression in the human vascular endothelial cell line EAhy926. The anionic bubble lipopolyplexes, however, delivered pDNA into cells without endocytosis and showed markedly high gene expression following US exposure. The anionic bubble lipopolyplexes showed little cytotoxicity in EAhy926 cells and little aggregation with erythrocytes. Following intravenous administration into mice, the anionic bubble lipopolyplexes showed high levels of gene expression in the liver, kidney, and spleen only after US exposure to the abdominal area. The level of gene expression in liver non-parenchymal cells was significantly higher than that in parenchymal cells. In addition, the anionic bubble lipopolyplexes did not show any severe hepatic toxicity and did not enhance the production of proinflammatory cytokines. Overall, we have succeeded in preparing anionic bubble lipopolyplexes for efficient and safe transfection with US exposure in mice.
authors.affiliation: Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshidashimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan; Japan Society for the Promotion of Science (JSPS), Chiyoda-ku, Tokyo 102-8471, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Kurosaki
authors.affiliation: Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan. Electronic address: skawakam@nagasaki-u.ac.jp.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kawakami
authors.affiliation: Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshidashimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Higuchi
authors.affiliation: Department of Biopharmaceutics, School of Pharmaceutical Sciences, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Suzuki
authors.affiliation: Department of Biopharmaceutics, School of Pharmaceutical Sciences, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Maruyama
authors.affiliation: Department of Hospital Pharmacy, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sasaki
authors.affiliation: Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshidashimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Fumiyoshi
authors.initials: F
authors.lastname: Yamashita
authors.affiliation: Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshidashimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan; Institute of Integrated Cell-Material Sciences (iCeMS), Kyoto University, Yoshida-Ushinomiya-cho, Sakyo-ku, Kyoto 606-8302, Japan. Electronic address: hashidam@pharm.kyoto-u.ac.jp.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Hashida
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000008:administration & dosage / Q000737:chemistry; D005260:Female; D015870:Gene Expression; D018014:Gene Transfer Techniques; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008081:Liposomes / Q000737:chemistry; D008099:Liver / Q000378:metabolism; D008156:Luciferases / Q000235:genetics; D051379:Mice; D008813:Mice, Inbred ICR; D011108:Polymers / Q000737:chemistry; D013154:Spleen / Q000378:metabolism; D014465:Ultrasonics / Q000379:methods*
chemical_list: D008081:Liposomes; D011108:Polymers; D004247:DNA; D008156:Luciferases
keywords: Biocompatibility; DNA; Liposomes; Self assembly; Sonoporation; Transfection