Article Chemistry Dug Delivery System Year 2013

Development of high boron content liposomes and their promising antitumor effect for neutron capture therapy of cancers

Bioconjugate Chemistry, 2013

Authors:   Hayato Koganei,Manabu Ueno,Shoji Tachikawa,Lisa Tasaki,Hyun Ban,Minoru Suzuki,Kouichi Shiraishi,Kumi Kawano,Masayuki Yokoyama,Yoshie Maitani,Koji Ono,Hiroyuki Nakamura
Journal: Bioconjugate Chemistry
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) × 1012 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). © 2012 American Chemical Society.