Development of High Boron Content Liposomes and Their Promising Antitumor Effect for Neutron Capture Therapy of Cancers
Development of High Boron Content Liposomes and Their Promising Antitumor Effect for Neutron Capture Therapy of Cancers
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DOI：
10.1021/bc300527n
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发表时间：
2013-01-01
影响因子：
4.7
通讯作者：
Nakamura, Hiroyuki
中科院分区：
文献类型：
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作者：
Koganei, Hayato;Ueno, Manabu;Nakamura, Hiroyuki
研制了包埋10%双硬脂酰化硼脂(DSBL)的硫代十一氢十二硼酸盐(BSH)脂质体，作为中子俘获治疗的硼载体。目前的方法是独特的，因为除了它的包封剂外，脂质体外壳本身也具有杀细胞的潜力。包埋BSH的10%DSBL脂质体具有高的硼含量(B/P比：2.6)，使我们能够制备出硼浓度为5000ppm的脂质体溶液。BSH包裹的10%DSBL脂质体对肿瘤显示出良好的硼传递效果：在50、30和15 mg B/kg剂量下，硼浓度分别达到174、93和32ppm。将Magnescope也包裹在10%的DSBL脂质体中，利用磁共振成像技术实时测量包裹的DSBL脂质体在活体中的生物分布。BSH包埋10%DSBL脂质体在15 mg B/kg剂量下仍有明显的抗肿瘤作用，热中子照射3周后肿瘤完全消失(1.5~1.8×10(12)中子/cm~2)。目前的结果使我们能够将脂质体的总剂量与包裹BSH的脂质体相比减少到不到五分之一，而不会降低硼中子俘获疗法(BNCT)的疗效。
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) x 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).