TY - GEN

T1 - Polymer-stabilized elemental boron nanoparticles for BNCT: cell irradiation experiments

AU - Заборонок, Александр Анатольевич

AU - Успенский, С.А.

AU - Хаптаханова, П.А.

AU - Bekarevich, R.

AU - Мечетина, Людмила Васильевна

AU - Волкова, Ольга Юрьевна

AU - Касатов, Дмитрий Александрович

AU - Щудло, Иван Михайлович

AU - Таскаев, Сергей Юрьевич

AU - Mathis, B.J.

AU - Каныгин, Владимир Владимирович

AU - Matsumura, А.

N1 - Conference code: 19

PY - 2021

Y1 - 2021

N2 - The boron compounds currently used in clinical and preclinical BNCT experiments, BSH and BPA, do not meet all the desired criteria for ideal treatment. Their imperfections motivate scientists to search for new solutions that better meet the requirements, one of which is the delivery of sufficient amounts of boron to tumor cells to reach a 10B concentration of ≥ 20-30 µg/g in tumor tissue. Without addressing tumor-targeting issues, loading tumor tissue with a sufficient amount of boron can be solved using nanoparticles that contain large numbers of boron atoms per particle, compared to 1 or 12 boron atoms per molecule of BPA or BSH, respectively. Thus, a 3 nm nanoparticle contains ~ 120 thousand 10B atoms and a 50 nm nanoparticle can deliver about 2 million 10B atoms. Here. we report on irradiation experiments using elemental boron nanoparticles (eBNPs) synthesized by a new method of cascade ultrasonic dispersion/destruction of elemental boron micron particles (10-20 microns) in an aqueous medium and stabilized with hydroxyethyl cellulose. BPA was used as a control. Transmission electron microscopy was used for particle visualization. Cytotoxicity analysis by MTS assay showed no obvious toxicity up to high nanoparticle concentrations in T98 human glioma cells. For irradiation experiments, the cells were incubated with nanoparticles or BPA in different concentrations for 24 hours, washed with PBS, trypsinized, centrifuged, collected, and then placed in 1ml plastic vials in the medium they were incubated with to avoid BPA leakage from the cells. The plastic vials with cells were placed in a plexiglass phantom to imitate the human head and provide the maximum thermal neutron fluence at the level of the vials. Neutron irradiation was performed at an accelerator-based neutron source with a subsequent colony-forming assay to evaluate cell survival. Cell-survival curves were fit to the linear-quadratic (LQ) model and radiobiological parameters were calculated.The synthesized nanoparticles demonstrated tumor cell-killing effects significantly superior to those demonstrated by BPA using the same boron concentrations in the incubation medium. These preliminary results show the superiority of nanoparticle-based boron delivery for BNCT and warrant further tumor targeting-oriented modifications of the synthesized particle and subsequent in vivo experiments.

AB - The boron compounds currently used in clinical and preclinical BNCT experiments, BSH and BPA, do not meet all the desired criteria for ideal treatment. Their imperfections motivate scientists to search for new solutions that better meet the requirements, one of which is the delivery of sufficient amounts of boron to tumor cells to reach a 10B concentration of ≥ 20-30 µg/g in tumor tissue. Without addressing tumor-targeting issues, loading tumor tissue with a sufficient amount of boron can be solved using nanoparticles that contain large numbers of boron atoms per particle, compared to 1 or 12 boron atoms per molecule of BPA or BSH, respectively. Thus, a 3 nm nanoparticle contains ~ 120 thousand 10B atoms and a 50 nm nanoparticle can deliver about 2 million 10B atoms. Here. we report on irradiation experiments using elemental boron nanoparticles (eBNPs) synthesized by a new method of cascade ultrasonic dispersion/destruction of elemental boron micron particles (10-20 microns) in an aqueous medium and stabilized with hydroxyethyl cellulose. BPA was used as a control. Transmission electron microscopy was used for particle visualization. Cytotoxicity analysis by MTS assay showed no obvious toxicity up to high nanoparticle concentrations in T98 human glioma cells. For irradiation experiments, the cells were incubated with nanoparticles or BPA in different concentrations for 24 hours, washed with PBS, trypsinized, centrifuged, collected, and then placed in 1ml plastic vials in the medium they were incubated with to avoid BPA leakage from the cells. The plastic vials with cells were placed in a plexiglass phantom to imitate the human head and provide the maximum thermal neutron fluence at the level of the vials. Neutron irradiation was performed at an accelerator-based neutron source with a subsequent colony-forming assay to evaluate cell survival. Cell-survival curves were fit to the linear-quadratic (LQ) model and radiobiological parameters were calculated.The synthesized nanoparticles demonstrated tumor cell-killing effects significantly superior to those demonstrated by BPA using the same boron concentrations in the incubation medium. These preliminary results show the superiority of nanoparticle-based boron delivery for BNCT and warrant further tumor targeting-oriented modifications of the synthesized particle and subsequent in vivo experiments.

UR - https://elibrary.ru/item.asp?id=47962271&pff=1

M3 - Conference contribution

SP - 160

BT - 19th International Congress on Neutron Capture Therapy Granada, Spain, September 27th - October 1st, 2021. Book of Abstacts

PB - International Atomic Energy Agency

CY - Вена

T2 - 19th International Congress on Neutron Capture Therapy

Y2 - 27 September 2021 through 1 October 2021

ER -