Shelly K, Feakes D A, Hawthorne M F, Schmidt P G, Krisch T A, Bauer W F
Department of Chemistry, University of California, Los Angeles 90024.
Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):9039-43. doi: 10.1073/pnas.89.19.9039.
The successful treatment of cancer by boron neutron-capture therapy (BNCT) requires the selective concentration of boron-10 within malignant tumors. The potential of liposomes to deliver boron-rich compounds to tumors has been assessed by the examination of the biodistribution of boron delivered by liposomes in tumor-bearing mice. Small unilamellar vesicles with mean diameters of 70 nm or less, composed of a pure synthetic phospholipid (distearoyl phosphatidylcholine) and cholesterol, have been found to stably encapsulate high concentrations of water-soluble ionic boron compounds. The hydrolytically stable borane anions B10H10(2-), B12H11SH2-, B20H17OH4-, B20H19(3-), and the normal form and photoisomer of B20H18(2-) were encapsulated in liposomes as their soluble sodium salts. The tissue concentration of boron in tumor-bearing mice was measured at several time points over 48 h after i.v. injection of emulsions of liposomes containing the borane anions. Although the boron compounds used do not exhibit an affinity for tumors and are normally rapidly cleared from the body, liposomes were observed to selectively deliver the borane anions to tumors. The highest tumor concentrations achieved reached the therapeutic range (greater than 15 micrograms of boron per g of tumor) while maintaining high tumor-boron/blood-boron ratios (greater than 3). The most favorable results were obtained with the two isomers of B20H18(2-). These boron compounds have the capability to react with intracellular components after they have been deposited within tumor cells by the liposome, thereby preventing the borane ion from being released into blood.
通过硼中子俘获疗法（BNCT）成功治疗癌症需要在恶性肿瘤内选择性地富集硼 - 10。通过检查脂质体递送的硼在荷瘤小鼠体内的生物分布，评估了脂质体将富含硼的化合物递送至肿瘤的潜力。已发现由纯合成磷脂（二硬脂酰磷脂酰胆碱）和胆固醇组成、平均直径为70纳米或更小的小单层囊泡能够稳定地包封高浓度的水溶性离子硼化合物。水解稳定的硼烷阴离子B10H10(2-)、B12H11SH2-、B20H17OH4-、B20H19(3-)以及B20H18(2-)的正常形式和光异构体以其可溶性钠盐的形式被包封在脂质体中。在静脉注射含有硼烷阴离子的脂质体乳剂后的48小时内的多个时间点，测量了荷瘤小鼠体内硼的组织浓度。尽管所使用的硼化合物对肿瘤没有亲和力且通常会迅速从体内清除，但观察到脂质体能够将硼烷阴离子选择性地递送至肿瘤。达到的最高肿瘤浓度达到了治疗范围（每克肿瘤中硼含量大于15微克），同时保持了高的肿瘤 - 硼/血液 - 硼比率（大于3）。使用B20H18(2-)的两种异构体获得了最有利的结果。这些硼化合物在通过脂质体沉积在肿瘤细胞内后能够与细胞内成分发生反应，从而防止硼烷离子释放到血液中。
