包裹十氢十硼酸根 -（¹⁰）B（GB - 10）的转铁蛋白悬垂型聚乙二醇脂质体作为硼中子俘获疗法的（¹⁰）B载体的潜力。

The potential of transferrin-pendant-type polyethyleneglycol liposomes encapsulating decahydrodecaborate-(10)B (GB-10) as (10)B-carriers for boron neutron capture therapy.

作者信息

Masunaga Shin-Ichiro, Kasaoka Satoshi, Maruyama Kazuo, Nigg David, Sakurai Yoshinori, Nagata Kenji, Suzuki Minoru, Kinashi Yuko, Maruhashi Akira, Ono Koji

机构信息

Particle Radiation Oncology Research Laboratory, Kyoto University, Kumatori, Osaka, Japan.

出版信息

Int J Radiat Oncol Biol Phys. 2006 Dec 1;66(5):1515-22. doi: 10.1016/j.ijrobp.2006.08.028.

DOI:10.1016/j.ijrobp.2006.08.028

PMID:17126210

Abstract

PURPOSE

To evaluate GB-10-encapsulating transferrin (TF)-pendant-type polyethyleneglycol (PEG) liposomes as tumor-targeting (10)B-carriers for boron neutron capture therapy.

METHODS AND MATERIALS

A free mercaptoundecahydrododecaborate-(10)B (BSH) or decahydrodecaborate-(10)B (GB-10) solution, bare liposomes, PEG liposomes, or TF-PEG liposomes were injected into SCC VII tumor-bearing mice, and (10)B concentrations in the tumors and normal tissues were measured by gamma-ray spectrometry. Meanwhile, tumor-bearing mice were continuously given 5-bromo-2'-deoxyuridine (BrdU) to label all intratumor proliferating cells, then injected with these (10)B-carriers containing BSH or GB-10 in the same manner. Right after thermal neutron irradiation, the response of quiescent (Q) cells was assessed in terms of the micronucleus frequency using immunofluorescence staining for BrdU. The frequency in the total tumor cells was determined from the BrdU nontreated tumors.

RESULTS

Transferrin-PEG liposomes showed a prolonged retention in blood circulation, low uptake by reticuloendothelial system, and the most enhanced accumulation of (10)B in solid tumors. In general, the enhancing effects were significantly greater in total cells than Q cells. In both cells, the enhancing effects of GB-10-containing (10)B-carriers were significantly greater than BSH-containing (10)B-carriers, whether loaded in free solution or liposomes. In both cells, whether BSH or GB-10 was employed, the greatest enhancing effect was observed with TF-PEG liposomes followed in decreasing order by PEG liposomes, bare liposomes, and free BSH or GB-10 solution. In Q cells, the decrease was remarkable between PEG and bare liposomes.

CONCLUSIONS

In terms of biodistribution characteristics and tumor cell-killing effect as a whole, including Q cells, GB-10 TF-PEG liposomes were regarded as promising (10)B-carriers.

摘要

目的

评估包裹GB - 10的转铁蛋白（TF）- 悬垂型聚乙二醇（PEG）脂质体作为硼中子俘获疗法的肿瘤靶向（¹⁰）B载体。

方法和材料

将游离的巯基十一氢十二硼酸盐 - （¹⁰）B（BSH）或十氢十硼酸盐 - （¹⁰）B（GB - 10）溶液、空白脂质体、PEG脂质体或TF - PEG脂质体注射到荷SCC VII肿瘤的小鼠体内，通过γ射线光谱法测量肿瘤和正常组织中的（¹⁰）B浓度。同时，给荷瘤小鼠连续给予5 - 溴 - 2'-脱氧尿苷（BrdU）以标记所有肿瘤内增殖细胞，然后以相同方式注射这些含有BSH或GB - 10的（¹⁰）B载体。热中子照射后，使用针对BrdU的免疫荧光染色，根据微核频率评估静止（Q）细胞的反应。总肿瘤细胞中的频率由未用BrdU处理的肿瘤确定。

结果

转铁蛋白 - PEG脂质体在血液循环中保留时间延长，网状内皮系统摄取率低，并且在实体瘤中（¹⁰）B的积累增强最为明显。一般来说，总细胞中的增强作用明显大于Q细胞中的增强作用。在两种细胞中，无论是游离溶液还是脂质体中负载的含GB - 10的（¹⁰）B载体的增强作用均明显大于含BSH的（¹⁰）B载体。在两种细胞中，无论使用BSH还是GB - 10，观察到TF - PEG脂质体的增强作用最大，其次按降序排列为PEG脂质体、空白脂质体和游离BSH或GB - 10溶液。在Q细胞中，PEG脂质体和空白脂质体之间的下降显著。