Hyaluronic acid as a potential boron carrier for BNCT: Preliminary evaluation

Zaboronok, Alexander; Yamamoto, Tetsuya; Nakai, Kei; Yoshida, Fumiyo; Успенский, С. А.; Selyanin, Mikhail A.; Зеленецкий, А. Н.; Matsumura, Akira

doi:10.1016/j.apradiso.2015.08.020

Cited by 10 publications

(7 citation statements)

References 16 publications

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“…The animals were sacrificed at different time intervals after compound injection (1, 2, 3, and 4 h for BSH and BPA; 24 h for liposomal BSH). Blood, tumor, brain, kidney and liver tissues were sampled and processed as previously reported (Zaboronok et al 2015) and analyzed for boron concentration using an iCAP6500 ICP optical emission spectrometer (ThermoFisher Scientific, Inc., Waltham, MA, USA. ).…”

Section: Boron Compound Biodistributionmentioning

confidence: 99%

Accelerator-based boron neutron capture therapy for malignant glioma: a pilot neutron irradiation study using boron phenylalanine, sodium borocaptate and liposomal borocaptate with a heterotopic U87 glioblastoma model in SCID mice

Zavjalov

Zaboronok

Kanygin

et al. 2020

International Journal of Radiation Biology

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Section: Boron Compound Biodistributionmentioning

confidence: 99%

Accelerator-based boron neutron capture therapy for malignant glioma: a pilot neutron irradiation study using boron phenylalanine, sodium borocaptate and liposomal borocaptate with a heterotopic U87 glioblastoma model in SCID mice

Zavjalov

Zaboronok

Kanygin

et al. 2020

International Journal of Radiation Biology

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“…Regarding BPA, we can be guided by previously obtained data, but experimental conditions, including irradiation settings, may differ. When using standard, previously effective methods of sample preparation and analysis of boron content by inductively coupled plasma atomic emission spectroscopy (ICP-AES [70]), we could not achieve complete dissolution of the stabilized boron nanoparticles in the acid medium. This may be due to the resistance of HEC to oxidation and the prevention of nanoparticle contact with the external environment, which may in turn, along with difficulties in determining the boron concentration, modulate the stability of synthesized complexes.…”

Section: Discussionmentioning

confidence: 88%

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

et al. 2022

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Sufficient boron-10 isotope (10B) accumulation by tumor cells is one of the main requirements for successful boron neutron capture therapy (BNCT). The inability of the clinically registered 10B-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 10B/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 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.

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“…Since membrane trafficking of small molecules and nanoparticles differs [ 39 , 40 , 41 , 42 ], a more reliable way to deliver larger amounts of both diagnostic and therapeutic components might be realized through combinations of gold and boron in single nanoparticles, making it easier to track them in the body and to determine pharmacokinetics, pharmacodynamics, and tolerability as well as therapeutic and diagnostic effectiveness after neutron irradiation. As non-covalently combined substances (e.g., chelated compounds) can be detached from each other and transported separately (binding to blood proteins) while maintaining stability in aqueous solutions [ 21 , 45 ], covalent binding of boron and gold or binding in one crystal lattice might be necessary for such complex compounds.…”

Section: Discussionmentioning

confidence: 99%

“…Boron and gold concentration in T98G cells was evaluated by ICP-AES according to previously adopted protocols [ 19 , 21 ]. After 24-h incubation with AuNPs (50 µg gold/mL) or BPA (10, 20, 40 µg boron/mL), the cells were washed with PBS, trypsinized, and counted.…”

Section: Methodsmentioning

confidence: 99%

“…The short alpha-particle pathway during BNCT (~10µm) that remains within the tumor cell diameter and spares normal cells from radiation also limits dosimetry options, as there is no essential extracellular energy release and calculating the boron-related absorbed dose is difficult. For that reason, golden foils are typically used for dosimetry [16,17] and placed in proximity to tissues or samples, where they activate after irradiation and provide indirect absorbed-dose measurement by detecting 411 keV gamma-rays released from the 198 Au isotope with a half-life of 2.69517 (21) days [18]. Though widely applied, such a dosimetry method cannot provide data on actual neutron capture inside tumor cells.…”

Section: Introductionmentioning

confidence: 99%

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Gold Nanoparticles Permit In Situ Absorbed Dose Evaluation in Boron Neutron Capture Therapy for Malignant Tumors

et al. 2021

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Boron neutron capture therapy (BNCT) is an anticancer modality realized through 10B accumulation in tumor cells, neutron irradiation of the tumor, and decay of boron atoms with the release of alpha-particles and lithium nuclei that damage tumor cell DNA. As high-LET particle release takes place inside tumor cells absorbed dose calculations are difficult, since no essential extracellular energy is emitted. We placed gold nanoparticles inside tumor cells saturated with boron to more accurately measure the absorbed dose. T98G cells accumulated ~50 nm gold nanoparticles (AuNPs, 50 µg gold/mL) and boron-phenylalanine (BPA, 10, 20, 40 µg boron-10/mL), and were irradiated with a neutron flux of 3 × 108 cm−2s−1. Gamma-rays (411 keV) emitted by AuNPs in the cells were measured by a spectrometer and the absorbed dose was calculated using the formula D = (k × N × n)/m, where D was the absorbed dose (GyE), k—depth-related irradiation coefficient, N—number of activated gold atoms, n—boron concentration (ppm), and m—the mass of gold (g). Cell survival curves were fit to the linear-quadratic (LQ) model. We found no influence from the presence of the AuNPs on BNCT efficiency. Our approach will lead to further development of combined boron and high-Z element-containing compounds, and to further adaptation of isotope scanning for BNCT dosimetry.

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Hyaluronic acid as a potential boron carrier for BNCT: Preliminary evaluation

Cited by 10 publications

References 16 publications

Accelerator-based boron neutron capture therapy for malignant glioma: a pilot neutron irradiation study using boron phenylalanine, sodium borocaptate and liposomal borocaptate with a heterotopic U87 glioblastoma model in SCID mice

Accelerator-based boron neutron capture therapy for malignant glioma: a pilot neutron irradiation study using boron phenylalanine, sodium borocaptate and liposomal borocaptate with a heterotopic U87 glioblastoma model in SCID mice

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

Gold Nanoparticles Permit In Situ Absorbed Dose Evaluation in Boron Neutron Capture Therapy for Malignant Tumors

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