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Ultrasound-mediated gene delivery systems by AG73-modified bubble liposomes

Authors

  • Yoichi Negishi,

    Corresponding author
    • Department of Drug Delivery and Molecular Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan
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    • This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com

  • Yuka Tsunoda,

    1. Department of Drug Delivery and Molecular Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan
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    • This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com

  • Nobuhito Hamano,

    1. Department of Drug Delivery and Molecular Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan
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  • Daiki Omata,

    1. Laboratory of Drug and Gene Delivery, Faculty of Pharma-Sciences, Teikyo University, Tokyo, Japan
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  • Yoko Endo-Takahashi,

    1. Department of Drug Delivery and Molecular Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan
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  • Ryo Suzuki,

    1. Laboratory of Drug and Gene Delivery, Faculty of Pharma-Sciences, Teikyo University, Tokyo, Japan
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  • Kazuo Maruyama,

    1. Laboratory of Drug and Gene Delivery, Faculty of Pharma-Sciences, Teikyo University, Tokyo, Japan
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  • Motoyoshi Nomizu,

    1. Department of Clinical Biochemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan
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  • Yukihiko Aramaki

    1. Department of Drug Delivery and Molecular Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan
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  • Yoichi Negishi and Yuka Tsunoda contributed equally to this work.

Correspondence to: Yoichi Negishi, Department of Drug Delivery and Molecular Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan; e-mail: negishi@toyaku.ac.jp

ABSTRACT

Targeted gene delivery to neovascular vessels in tumors is considered a promising strategy for cancer therapy. We previously reported that “Bubble liposomes” (BLs), which are ultrasound (US) imaging gas-encapsulating liposomes, were suitable for US imaging and gene delivery. When BLs are exposed to US, the bubble is destroyed, creating a jet stream by cavitation, and resulting in the instantaneous ejection of extracellular plasmid DNA (pDNA) or other nucleic acids into the cytosol. We developed AG73 peptide-modified Bubble liposomes (AG73-BL) as a targeted US contrast agent, which was designed to attach to neovascular tumor vessels and to allow specific US detection of angiogenesis (Negishi et al., Biomaterials 2013, 34, 501–507). In this study, to evaluate the effectiveness of AG73-BL as a gene delivery tool for neovascular vessels, we examined the gene transfection efficiency of AG73-BL with US exposure in primary human endothelial cells (HUVEC). The transfection efficiency was significantly enhanced if the AG73-BL attached to the HUVEC was exposed to US compared to the BL-modified with no peptide or scrambled peptide. In addition, the cell viability was greater than 80% after transfection with AG73-BL. These results suggested that after the destruction of the AG73-BL with US exposure, a cavitation could be effectively induced by the US exposure against AG73-BL binding to the cell surface of the HUVEC, and the subsequent gene delivery into cells could be enhanced. Thus, AG73-BL may be useful for gene delivery as well as for US imaging of neovascular vessels. © 2013 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 100: 402–407, 2013.

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