Development of anionic bubble lipopolyplexes for efficient and safe gene transfection with ultrasound exposure in mice

JOURNAL OF CONTROLLED RELEASE

卷:176

Article

Kurosaki, Tomoaki^1,2  Kawakami, Shigeru³  Higuchi, Yuriko¹  Suzuki, Ryo⁴  Maruyama, Kazuo⁴  Sasaki, Hitoshi⁵  Yamashita, Fumiyoshi¹  Hashida, Mitsuru^1,6 

[1] Kyoto Univ, Grad Sch Pharmaceut Sci, Dept Drug Delivery Res, Sakyo Ku, Kyoto 6068501, Japan

[2] Japan Soc Promot Sci, Chiyoda Ku, Tokyo 1028471, Japan

[3] Nagasaki Univ, Grad Sch Biomed Sci, Nagasaki 8528521, Japan

[4] Teikyo Univ, Sch Pharmaceut Sci, Dept Biopharmaceut, Itabashi Ku, Tokyo 1738605, Japan

[5] Nagasaki Univ Hosp, Dept Hosp Pharm, Nagasaki 8528501, Japan

[6] Kyoto Univ, Inst Integrated Cell Mat Sci iCeMS, Sakyo Ku, Kyoto 6068302, Japan

关键词: DNA;    Transfection;    Self assembly;    Biocompatibility;    Liposomes;    Sonoporation;   

DOI  :  10.1016/j.jconrel.2013.12.023

来源: Elsevier

【 摘 要 】

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 450-600 nm 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. (C) 2013 Elsevier B. V. All rights reserved.

【 授权许可】

Free