A novel DDS strategy, "dual-targeting", and its application for antineovascular therapy.
Dual-targeting liposomes modified with Ala-Pro-Arg-Pro-Gly (APRPG) and Gly-Asn-Gly-Arg-Gly (GNGRG) peptides were developed. They remarkably associated to growing human umbilical vein endothelial cells (HUVECs) compared with single-targeting liposomes modified with APRPG or GNGRG. Doxorubicin (DOX) encapsulated in the dual-targeting liposomes significantly suppressed the growth of HUVECs compared with that in single-targeting liposomes. The dual-targeting liposomes containing DOX strongly suppressed tumor growth in Colon26 NL-17 carcinoma-bearing mice. Confocal microscopic data indicated that this anticancer effect was brought by the association of these liposomes to angiogenic vessels in the tumor. These findings suggest that "dual-targeting" would be a hopeful method for targeting therapies.
Murase
Yuki
Y
Department of Medical Biochemistry and Global COE Program, Graduate School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
Asai
Tomohiro
T
Katanasaka
Yasufumi
Y
Sugiyama
Tomoki
T
Shimizu
Kosuke
K
Maeda
Noriyuki
N
Oku
Naoto
N
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002626:Chemistry, Pharmaceutical; D002784:Cholesterol / Q000737:chemistry; D003110:Colonic Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007275:Injections, Intravenous; D008081:Liposomes; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism*; D010316:Particle Size; D010713:Phosphatidylcholines / Q000737:chemistry; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D014018:Tissue Distribution
D020533:Angiogenesis Inhibitors; D000903:Antibiotics, Antineoplastic; D008081:Liposomes; D009842:Oligopeptides; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; C490869:alanyl-prolyl-arginyl-prolyl-glycine; C038089:1,2-distearoylphosphatidylethanolamine; D011092:Polyethylene Glycols; D004317:Doxorubicin; D002784:Cholesterol; C010942:1,2-distearoyllecithin