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).

closo-Dodecaborate-encapsulating liposomes were developed as boron delivery vehicles for neutron capture therapy. The use of spermidinium as a counter cation of closo-dodecaborates was essential not only for the preparation of high boron content liposome solutions but also for efficient boron delivery to tumors.

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High-boron-content compounds, 8, 10, and 13, were designed and synthesized as boron agents encapsulated in liposomes by the Hüisgen click cycloaddition of closo-dodecaborate-containing azides and alkynes. These compounds have relatively low cytotoxicities and their GI 50 values for B16, CT26, and HeLa cells are higher than 0.14 mM, indicating toxicities similar to that of BSH. High-boron-content liposomes were prepared using 13, which has the largest number of boron atoms in a molecule among the synthesized compounds. The final boron concentration in 13-encapsulating liposomes reached 11.0 Â 10 3 ppm with a B/P ratio of 5.1. A significantly high tumor boron accumulation (72.2 ppm) was observed in tumor-bearing mice 36 h after the injection of 13-encapsulating liposomes at a dose of 15 mgB kg À1 body weight with the tumor/blood (T/B) ratio of approximately 14.