title: Development of high boron content liposomes and their promising antitumor effect for neutron capture therapy of cancers.
abstract: Mercaptoundecahydrododecaborate (BSH)-encapsulating 10% distearoyl boron lipid (DSBL) liposomes were developed as a boron delivery vehicle for neutron capture therapy. The current approach is unique because the liposome shell itself possesses cytocidal potential in addition to its encapsulated agents. BSH-encapsulating 10% DSBL liposomes have high boron content (B/P ratio: 2.6) that enables us to prepare liposome solution with 5000 ppm boron concentration. BSH-encapsulating 10% DSBL liposomes displayed excellent boron delivery efficacy to tumor: boron concentrations reached 174, 93, and 32 ppm at doses of 50, 30, and 15 mg B/kg, respectively. Magnescope was also encapsulated in the 10% DSBL liposomes and the real-time biodistribution of the Magnescope-encapsulating DSBL liposomes was measured in a living body using MRI. Significant antitumor effect was observed in mice injected with BSH-encapsulating 10% DSBL liposomes even at the dose of 15 mg B/kg; the tumor completely disappeared three weeks after thermal neutron irradiation ((1.5-1.8) × 10(12) neutrons/cm(2)). The current results enabled us to reduce the total dose of liposomes to less than one-fifth compared with that of the BSH-encapsulating liposomes without reducing the efficacy of boron neutron capture therapy (BNCT).
authors.affiliation: Department of Chemistry, Faculty of Science, Gakushuin University, Mejiro, Toshima-ku, Tokyo 171-8588, Japan.
authors.forename: Hayato
authors.initials: H
authors.lastname: Koganei
authors.forename: Manabu
authors.initials: M
authors.lastname: Ueno
authors.forename: Shoji
authors.initials: S
authors.lastname: Tachikawa
authors.forename: Lisa
authors.initials: L
authors.lastname: Tasaki
authors.forename: Hyun Seung
authors.initials: HS
authors.lastname: Ban
authors.forename: Minoru
authors.initials: M
authors.lastname: Suzuki
authors.forename: Kouichi
authors.initials: K
authors.lastname: Shiraishi
authors.forename: Kumi
authors.initials: K
authors.lastname: Kawano
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yokoyama
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Maitani
authors.forename: Koji
authors.initials: K
authors.lastname: Ono
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakamura
mesh_terms: D000818:Animals; D001894:Borohydrides / Q000737:chemistry*; D001895:Boron / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D016754:Boron Neutron Capture Therapy / Q000379:methods*; D005260:Female; D007554:Isotopes / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D008055:Lipids / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D013438:Sulfhydryl Compounds / Q000737:chemistry*
chemical_list: D001894:Borohydrides; D007554:Isotopes; D008055:Lipids; D008081:Liposomes; D013438:Sulfhydryl Compounds; C014651:mercaptoundecahydrododecaborate; D001895:Boron