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 ex...

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Bibliographic Details
Published in:Biopolymers 2013-07, Vol.100 (4), p.402-407
Main Authors: Negishi, Yoichi, Tsunoda, Yuka, Hamano, Nobuhito, Omata, Daiki, Endo-Takahashi, Yoko, Suzuki, Ryo, Maruyama, Kazuo, Nomizu, Motoyoshi, Aramaki, Yukihiko
Format: Article
Language:English
Subjects:
AG73
Bubble liposome
gene delivery
Gene Transfer Techniques
Genetic Therapy
Humans
Liposomes
Plasmids
syndecan
Transfection
Ultrasonics
ultrasound imaging
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Summary: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.
ISSN:0006-3525
1097-0282
DOI:10.1002/bip.22246