title: Transferrin-loaded nido-carborane liposomes: tumor-targeting boron delivery system for neutron capture therapy.
abstract: The nido-carborane lipid 2 as a double-tailed boron lipid was synthesized from heptadecanol in five steps. The lipid 2 formed stable liposomes at 25% molar ratio toward DSPC with cholesterol. Transferrin was able to be introduced on the surface of boron liposomes (Tf(+)-PEG-CL liposomes) by the coupling of transferrin to the PEG-CO(2)H moieties of Tf(-)-PEG-CL liposomes. The biodistribution of Tf(+)-PEG-CL liposomes, in which (125)I-tyraminyl inulins were encapsulated, showed that Tf(+)-PEG-CL liposomes accumulated in tumor tissues and stayed there for a sufficiently long time to increase tumor/blood concentration ratio, although Tf(-)-PEG-CL liposomes were gradually released from tumor tissues with time. A boron concentration of 22 ppm in tumor tissues was achieved by the injection of Tf(+)-PEG-CL liposomes at 7.2 mg/kg body weight boron in tumor-bearing mice. After neutron irradiation, the average survival rate of mice not treated with Tf(+)-PEG-CL liposomes was 21 days, whereas that of the treated mice was 31 days. Longer survival rates were observed in the mice treated with Tf(+)-PEG-CL liposomes; one of them even survived for 52 days after BNCT.
authors.affiliation: Department of Chemistry, Faculty of Science, Gakushuin University, Tokyo 171-8588, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Miyajima
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakamura
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kuwata
authors.forename: Jong-Dae
authors.initials: JD
authors.lastname: Lee
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Masunaga
authors.forename: Koji
authors.initials: K
authors.lastname: Ono
authors.forename: Kazuo
authors.initials: K
authors.lastname: Maruyama
mesh_terms: D000818:Animals; D001896:Boron Compounds / Q000737:chemistry / Q000378:metabolism; D016754:Boron Neutron Capture Therapy / Q000379:methods*; D002417:Cattle; D005452:Fluoresceins / Q000737:chemistry / Q000378:metabolism; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D009369:Neoplasms / Q000378:metabolism / Q000628:therapy; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism; D015996:Survival Rate; D014168:Transferrin / Q000737:chemistry / Q000378:metabolism*
chemical_list: D001896:Boron Compounds; D005452:Fluoresceins; D008055:Lipids; D008081:Liposomes; D014168:Transferrin; D011092:Polyethylene Glycols; C007740:fluorexon