TY - JOUR

T1 - Polymer-Stabilized Elemental Boron Nanoparticles for Boron Neutron Capture Therapy: Initial Irradiation Experiments

AU - Zaboronok, Alexander

AU - Khaptakhanova, Polina

AU - Uspenskii, Sergey

AU - Bekarevich, Raman

AU - Mechetina, Ludmila

AU - Volkova, Olga

AU - Mathis, Bryan J.

AU - Kanygin, Vladimir

AU - Ishikawa, Eiichi

AU - Kasatova, Anna

AU - Kasatov, Dmitrii

AU - Shchudlo, Ivan

AU - Sycheva, Tatiana

AU - Taskaev, Sergey

AU - Matsumura, Akira

N1 - Funding Information: Funding: This work was supported by Grants-in-Aid for Scientific Research (C) JSPS KAKENHI [20K07672] and (B) [18H02909] the Japanese Ministry of Education, Culture, Sports, Science and Technology. Neutron generation was supported by the Russian Science Foundation, project No. 19-72-30005. The synthesis and stabilization of the boron nanoparticles and the DLS measurements (particle size and zeta potential) were funded by the Russian Foundation for Basic Research, project No. 20-33-90283. Determinations of the viscosity of the HEC solution were supported by the Ministry of Science and Higher Education of the Russian Federation, grant No. FFSM-2021-0006. Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2022/4

Y1 - 2022/4

N2 - Sufficient boron-10 isotope (10 B) accumulation by tumor cells is one of the main requirements for successful boron neutron capture therapy (BNCT). The inability of the clinically registered10 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 µg10 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 × 1012 /cm2 . The eBNPs significantly reduced colony-forming capacity in all studied cells during BNCT compared to BPA, verified by cell-survival curves fit to the linearquadratic 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.

AB - Sufficient boron-10 isotope (10 B) accumulation by tumor cells is one of the main requirements for successful boron neutron capture therapy (BNCT). The inability of the clinically registered10 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 µg10 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 × 1012 /cm2 . The eBNPs significantly reduced colony-forming capacity in all studied cells during BNCT compared to BPA, verified by cell-survival curves fit to the linearquadratic 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.

KW - accelerator-based neutron source

KW - boron neutron capture therapy

KW - elemental boron nanoparticles

KW - hydroxyethylcellulose

KW - polymer stabilization

UR - http://www.scopus.com/inward/record.url?scp=85128521808&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/c742eb87-d17d-33ea-a3ad-654f62b30741/

U2 - 10.3390/pharmaceutics14040761

DO - 10.3390/pharmaceutics14040761

M3 - Article

C2 - 35456595

AN - SCOPUS:85128521808

VL - 14

JO - Pharmaceutics

JF - Pharmaceutics

SN - 1999-4923

IS - 4

M1 - 761

ER -