title: Ultrasound-mediated gene delivery systems by AG73-modified Bubble liposomes.
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.
authors.affiliation: Department of Drug Delivery and Molecular Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Negishi
authors.forename: Yuka
authors.initials: Y
authors.lastname: Tsunoda
authors.forename: Nobuhito
authors.initials: N
authors.lastname: Hamano
authors.forename: Daiki
authors.initials: D
authors.lastname: Omata
authors.forename: Yoko
authors.initials: Y
authors.lastname: Endo-Takahashi
authors.forename: Ryo
authors.initials: R
authors.lastname: Suzuki
authors.forename: Kazuo
authors.initials: K
authors.lastname: Maruyama
authors.forename: Motoyoshi
authors.initials: M
authors.lastname: Nomizu
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Aramaki
mesh_terms: D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D008081:Liposomes; D010957:Plasmids; D014162:Transfection; D014465:Ultrasonics
chemical_list: D008081:Liposomes
keywords: AG73; Bubble liposome; gene delivery; syndecan; ultrasound imaging