Institute of Engineering Innovation, School of Engineering, The University of Tokyo, Tokyo, Japan;
Cooperative Unit of Medicine and Engineering, The University of Tokyo Hospital, Tokyo, Japan.
In Vivo. 2021 Nov-Dec;35(6):3125-3135. doi: 10.21873/invivo.12607.
BACKGROUND/AIM: Tumor cell destruction by boron neutron capture therapy (BNCT) is attributed to the nuclear reaction between B and thermal neutrons. The accumulation of B atoms in tumor cells without affecting adjacent healthy cells is crucial for effective BNCT. We previously reported that several types of liposomal boron delivery systems (BDS) delivered effective numbers of boron atoms to cancer tissues, and showed tumor-growth suppression after thermal neutron irradiation. In the present study, we examined the effects of BNCT after intra-arterial infusion of B-borono-dodecaborate (BSH) by liposomal BDS in rabbit hepatic cancer models.
We prepared BSH-entrapped transferrin-conjugated polyethylene glycol liposomes constructed with distearoyl-boron lipid (TF-PEG-DSBL), and performed thermal neutron irradiation at the Kyoto University Institute for Integrated Radiation and Nuclear Science after intra-arterial infusion into rabbit VX-2 hepatic tumors.
Concentrations of B in VX-2 tumors on delivery with TF-PEG-DSBL liposomes reached 25 ppm on day 3 after the injection. Tumor growth was suppressed by thermal neutron irradiation after intra-arterial injection of this BSH-containing liposomal BDS, without damage to normal cells.
The present results demonstrate the applicability of B-containing TF-PEG-DSBL liposomes as a novel intra-arterial boron carrier in BNCT for cancer.
背景/目的：硼中子俘获治疗（BNCT）通过硼与热中子之间的核反应来破坏肿瘤细胞。硼原子在肿瘤细胞中的积累而不影响相邻的健康细胞对于有效的 BNCT 至关重要。我们之前报道了几种类型的脂质体硼递药系统（BDS）将有效数量的硼原子递送到癌组织中，并在热中子照射后显示出肿瘤生长抑制作用。在本研究中，我们在兔肝癌模型中通过脂质体 BDS 经动脉内输注 B-硼代十二硼酸盐（BSH），研究了 BNCT 的效果。
我们制备了载有 BSH 的转铁蛋白-聚乙二醇脂质体，由二硬脂酰基硼脂质（TF-PEG-DSBL）构建，并在向兔 VX-2 肝癌肿瘤内动脉内输注后在京都大学综合辐射与核科学研究所进行热中子照射。
TF-PEG-DSBL 脂质体给药后第 3 天，VX-2 肿瘤中的硼浓度达到 25ppm。经动脉内注射这种含 BSH 的脂质体 BDS 后进行热中子照射，抑制了肿瘤生长，而对正常细胞没有损伤。
本研究结果表明，含硼的 TF-PEG-DSBL 脂质体作为 BNCT 治疗癌症的新型动脉内硼载体具有应用前景。
