pDNA-loaded Bubble liposomes as potential ultrasound imaging and gene delivery agents.
We have developed polyethyleneglycol (PEG)-modified liposomes (Bubble liposomes; BLs) that entrap ultrasound (US) contrast gas, and we have reported that the combination of BLs and US exposure was an effective tool for delivering pDNA and siRNA in vitro and in vivo. In this study, we prepared pDNA-loaded BLs using three types of cationic lipids to enhance the US imaging effect and the transfection efficiency via systemic injection. We investigated the US imaging abilities of these BLs, their protective effects on pDNA from serum component, and their transfection effects in vitro and in vivo. As a result, we demonstrated that the US imaging ability and transfection effect varied with lipid component and that p-BLs containing DSDAP could be the most stable and effective tool the among three types of p-BLs. Indeed, in ischemic muscle, p-BLs containing DSDAP could be detected using diagnostic US and could deliver bFGF-expressing pDNA using therapeutic US, leading to the induction of angiogenic factors and the improvement of blood flow. These results suggest that combining p-BLs with US exposure may be useful for stable US imaging and efficient gene delivery and may lead to the establishment of a theranostic approach, which is a combination of disease diagnosis and therapy.
Department of Drug Delivery and Molecular Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
Yoko
Y
Endo-Takahashi
Yoichi
Y
Negishi
Arisa
A
Nakamura
Daichi
D
Suzuki
Saori
S
Ukai
Katsutoshi
K
Sugimoto
Fuminori
F
Moriyasu
Norio
N
Takagi
Ryo
R
Suzuki
Kazuo
K
Maruyama
Yukihiko
Y
Aramaki
D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D004247:DNA / Q000737:chemistry*; D004195:Disease Models, Animal; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism; D005740:Gases / Q000737:chemistry; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006614:Hindlimb / Q000473:pathology; D007511:Ischemia / Q000473:pathology / Q000628:therapy; D008055:Lipids / Q000737:chemistry; D008081:Liposomes; D051379:Mice; D008813:Mice, Inbred ICR; D018482:Muscle, Skeletal / Q000473:pathology; D010957:Plasmids / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D034741:RNA, Small Interfering / Q000378:metabolism; D014162:Transfection; D014465:Ultrasonics / Q000295:instrumentation* / Q000379:methods*
D005740:Gases; D008055:Lipids; D008081:Liposomes; D034741:RNA, Small Interfering; D011092:Polyethylene Glycols; D005346:Fibroblast Growth Factors; D004247:DNA