Zaboronok Alexander, Khaptakhanova Polina, Uspenskii Sergey, Bekarevich Raman, Mechetina Ludmila, Volkova Olga, Mathis Bryan J, Kanygin Vladimir, Ishikawa Eiichi, Kasatova Anna, Kasatov Dmitrii, Shchudlo Ivan, Sycheva Tatiana, Taskaev Sergey, Matsumura Akira
Department of Neurosurgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Japan.
Laboratory of Medical and Biological Problems of BNCT, Department of Physics, Novosibirsk State University, 1 Pirogov Street, 630090 Novosibirsk, Russia.
Pharmaceutics. 2022 Mar 31;14(4):761. doi: 10.3390/pharmaceutics14040761.
Sufficient boron-10 isotope (B) accumulation by tumor cells is one of the main requirements for successful boron neutron capture therapy (BNCT). The inability of the clinically registered B-containing borophenylalanine (BPA) to maintain a high boron tumor concentration during neutron irradiation after a single injection has been partially solved by its continuous infusion; however, its lack of persistence has driven the development of new compounds that overcome the imperfections of BPA. We propose using elemental boron nanoparticles (eBNPs) synthesized by cascade ultrasonic dispersion and destruction of elemental boron microparticles and stabilized with hydroxyethylcellulose (HEC) as a core component of a novel boron drug for BNCT. These HEC particles are stable in aqueous media and show no apparent influence on U251, U87, and T98G human glioma cell proliferation without neutron beam irradiation. In BNCT experiments, cells incubated with eBNPs or BPA at an equivalent concentration of 40 µg B/mL for 24 h or control cells without boron were irradiated at an accelerator-based neutron source with a total fluence of thermal and epithermal neutrons of 2.685, 5.370, or 8.055 × 10/cm. The eBNPs significantly reduced colony-forming capacity in all studied cells during BNCT compared to BPA, verified by cell-survival curves fit to the linear-quadratic model and calculated radiobiological parameters, though the effect of both compounds differed depending on the cell line. The results of our study warrant further tumor targeting-oriented modifications of synthesized nanoparticles and subsequent in vivo BNCT experiments.
肿瘤细胞充分积累硼 - 10同位素(B)是成功进行硼中子俘获疗法(BNCT)的主要要求之一。临床注册的含硼硼替苯胺(BPA)在单次注射后,在中子辐照期间无法维持高硼肿瘤浓度的问题,已通过其持续输注得到部分解决;然而,其持久性不足促使人们开发新的化合物来克服BPA的缺陷。我们建议使用通过级联超声分散和破坏元素硼微粒并以羟乙基纤维素(HEC)稳定化合成的元素硼纳米颗粒(eBNPs)作为用于BNCT的新型硼药物的核心成分。这些HEC颗粒在水性介质中稳定,在没有中子束辐照的情况下,对U251、U87和T98G人胶质瘤细胞增殖没有明显影响。在BNCT实验中,将与eBNPs或BPA以40μg B/mL的等效浓度孵育24小时的细胞或不含硼的对照细胞,在基于加速器的中子源处以热中子和超热中子的总注量为2.685、5.370或8.055×10/cm进行辐照。与BPA相比,eBNPs在BNCT期间显著降低了所有研究细胞中的集落形成能力,通过拟合线性二次模型的细胞存活曲线和计算的放射生物学参数得到验证,尽管两种化合物的效果因细胞系而异。我们的研究结果需要对合成的纳米颗粒进行进一步的以肿瘤靶向为导向的修饰,并随后进行体内BNCT实验。