Systemic delivery of miR-126 by miRNA-loaded Bubble liposomes for the treatment of hindlimb ischemia.
Currently, micro RNA (miRNA) is considered an attractive target for therapeutic intervention. A significant obstacle to the miRNA-based treatments is the efficient delivery of miRNA to the target tissue. We have developed polyethylene glycol-modified liposomes (Bubble liposomes (BLs)) that entrap ultrasound (US) contrast gas and can serve as both plasmid DNA (pDNA) or small interfering RNA (siRNA) carriers and US contrast agents. In this study, we investigated the usability of miRNA-loaded BLs (mi-BLs) using a hindlimb ischemia model and miR-126. It has been reported that miR-126 promotes angiogenesis via the inhibition of negative regulators of VEGF signaling. We demonstrated that mi-BLs could be detected using diagnostic US and that mi-BLs with therapeutic US could deliver miR-126 to an ischemic hindlimb, leading to the induction of angiogenic factors and the improvement of blood flow. These results suggest that combining mi-BLs with US may be useful for US imaging and miRNA delivery.
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
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.
Yoichi
Y
Negishi
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.
Arisa
A
Nakamura
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.
Saori
S
Ukai
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.
Kotomi
K
Ooaku
Laboratory of Drug and Gene Delivery Research, Faculty of Pharma-Sciences, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan.
Yusuke
Y
Oda
Department of Gastroenterology and Hepatology, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan.
Katsutoshi
K
Sugimoto
Department of Gastroenterology and Hepatology, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan.
Fuminori
F
Moriyasu
Department of Applied Biochemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
Norio
N
Takagi
Laboratory of Drug and Gene Delivery Research, Faculty of Pharma-Sciences, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan.
Ryo
R
Suzuki
Laboratory of Drug and Gene Delivery Research, Faculty of Pharma-Sciences, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan.
Kazuo
K
Maruyama
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.
Yukihiko
Y
Aramaki
D043925:Angiogenesis Inducing Agents / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D002478:Cells, Cultured; D004337:Drug Carriers / Q000737:chemistry / Q000627:therapeutic use; D004912:Erythrocytes / Q000187:drug effects; D005786:Gene Expression Regulation; D006614:Hindlimb / Q000098:blood supply*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D007511:Ischemia / Q000188:drug therapy*; D008081:Liposomes / Q000737:chemistry / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D035683:MicroRNAs / Q000008:administration & dosage* / Q000627:therapeutic use*; D018482:Muscle, Skeletal / Q000098:blood supply; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011092:Polyethylene Glycols / Q000737:chemistry; D014162:Transfection / Q000379:methods; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
D043925:Angiogenesis Inducing Agents; D004337:Drug Carriers; D008081:Liposomes; C545201:MIRN126 microRNA, mouse; D035683:MicroRNAs; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D011092:Polyethylene Glycols