scholarly journals Synthesis and Evaluation of Dodecaboranethiol Containing Kojic Acid (KA-BSH) as a Novel Agent for Boron Neutron Capture Therapy

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1551 ◽  
Author(s):  
Koji Takeuchi ◽  
Yoshihide Hattori ◽  
Shinji Kawabata ◽  
Gen Futamura ◽  
Ryo Hiramatsu ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Neutron Irradiation ◽  
Boron Neutron Capture Therapy ◽  
Neutron Capture ◽  
Kojic Acid ◽  
Alpha Particles ◽  
Neutron Capture Therapy ◽  
Survival Times ◽  
Boron Neutron Capture ◽  
Biodistribution Studies

Boron neutron capture therapy (BNCT) is a form of tumor-cell selective particle irradiation using low-energy neutron irradiation of boron-10 (10B) to produce high-linear energy transfer (LET) alpha particles and recoiling 7Li nuclei (10B [n, alpha] 7Li) in tumor cells. Therefore, it is important to achieve the selective delivery of large amounts of 10B to tumor cells, with only small amounts of 10B to normal tissues. To develop practical materials utilizing 10B carriers, we designed and synthesized novel dodecaboranethiol (BSH)-containing kojic acid (KA-BSH). In the present study, we evaluated the effects of this novel 10B carrier on cytotoxicity, 10B concentrations in F98 rat glioma cells, and micro-distribution of KA-BSH in vitro. Furthermore, biodistribution studies were performed in a rat brain tumor model. The tumor boron concentrations showed the highest concentrations at 1 h after the termination of administration. Based on these results, neutron irradiation was evaluated at the Kyoto University Research Reactor Institute (KURRI) with KA-BSH. Median survival times (MSTs) of untreated and irradiated control rats were 29.5 and 30.5 days, respectively, while animals that received KA-BSH, followed by neutron irradiation, had an MST of 36.0 days (p = 0.0027, 0.0053). Based on these findings, further studies are warranted in using KA-BSH as a new B compound for malignant glioma.

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

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1490
Author(s):  
Alexander Zaboronok ◽  
Sergey Taskaev ◽  
Olga Volkova ◽  
Ludmila Mechetina ◽  
Anna Kasatova ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Tumor Cells ◽  
Boron Neutron Capture Therapy ◽  
Neutron Capture ◽  
Malignant Tumors ◽  
Absorbed Dose ◽  
Alpha Particles ◽  
Neutron Capture Therapy ◽  
Linear Quadratic ◽  
Boron Neutron Capture

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.

scholarly journals Gold Nanoparticles as Boron Carriers for Boron Neutron Capture Therapy: Synthesis, Radiolabelling and In vivo Evaluation

Molecules ◽  
2019 ◽  
Vol 24 (19) ◽  
pp. 3609 ◽  
Author(s):  
Pulagam ◽  
Gona ◽  
Gómez-Vallejo ◽  
Meijer ◽  
Zilberfain ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Mouse Model ◽  
Boron Neutron Capture Therapy ◽  
Neutron Capture ◽  
Neutron Capture Therapy ◽  
The Core ◽  
Boron Neutron Capture ◽  
Biodistribution Studies ◽  
Imaging Results

Background: Boron Neutron Capture Therapy (BNCT) is a binary approach to cancer therapy that requires accumulation of boron atoms preferentially in tumour cells. This can be achieved by using nanoparticles as boron carriers and taking advantage of the enhanced permeability and retention (EPR) effect. Here, we present the preparation and characterization of size and shape-tuned gold NPs (AuNPs) stabilised with polyethylene glycol (PEG) and functionalized with the boron-rich anion cobalt bis(dicarbollide), commonly known as COSAN. The resulting NPs were radiolabelled with 124I both at the core and the shell, and were evaluated in vivo in a mouse model of human fibrosarcoma (HT1080 cells) using positron emission tomography (PET). Methods: The thiolated COSAN derivatives for subsequent attachment to the gold surface were synthesized by reaction of COSAN with tetrahydropyran (THP) followed by ring opening using potassium thioacetate (KSAc). Iodination on one of the boron atoms of the cluster was also carried out to enable subsequent radiolabelling of the boron cage. AuNPs grafted with mPEG-SH (5 Kda) and thiolated COSAN were prepared by ligand displacement. Radiolabelling was carried out both at the shell (isotopic exchange) and at the core (anionic absorption) of the NPs using 124I to enable PET imaging. Results: Stable gold nanoparticles simultaneously functionalised with PEG and COSAN (PEG-AuNPs@[4]−) with hydrodynamic diameter of 37.8 ± 0.5 nm, core diameter of 19.2 ± 1.4 nm and ξ-potential of −18.0 ± 0.7 mV were obtained. The presence of the COSAN on the surface of the NPs was confirmed by Raman Spectroscopy and UV-Vis spectrophotometry. PEG-AuNPs@[4]− could be efficiently labelled with 124I both at the core and the shell. Biodistribution studies in a xenograft mouse model of human fibrosarcoma showed major accumulation in liver, lungs and spleen, and poor accumulation in the tumour. The dual labelling approach confirmed the in vivo stability of the PEG-AuNPs@[4]−. Conclusions: PEG stabilized, COSAN-functionalised AuNPs could be synthesized, radiolabelled and evaluated in vivo using PET. The low tumour accumulation in the animal model assayed points to the need of tuning the size and geometry of the gold core for future studies.

scholarly journals YC-1 sensitizes the antitumor effects of boron neutron capture therapy in hypoxic tumor cells

2020 ◽  
Vol 61 (4) ◽  
pp. 524-534
Author(s):  
Takaomi Harada ◽  
Katsumi Hirose ◽  
Yuki Wada ◽  
Mariko Sato ◽  
Koji Ichise ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Boron Neutron Capture Therapy ◽  
Neutron Capture ◽  
Neutron Capture Therapy ◽  
Boron Uptake ◽  
Antitumor Effects ◽  
Hypoxic Conditions ◽  
Boron Neutron Capture ◽  
Hypoxic Tumor ◽  
In Cells

Abstract The uptake of boron into tumor cells is a key factor in the biological effects of boron neutron capture therapy (BNCT). The uptake of boron agents is suppressed in hypoxic conditions, but the mechanism of hypoxia-induced modulation of suppression of boron uptake is not clear. Therefore, we evaluated whether hypoxia-inducible factor 1α (HIF-1α) contributes to attenuation of the antitumor effects of BNCT in hypoxic tumor cells. We also tested whether YC-1, a HIF-1α-targeting inhibitor, has therapeutic potential with BNCT. To elucidate the mechanism of attenuation of the effects of BNCT caused by hypoxia, deferoxamine (DFO) was used in experiments. Cells were incubated in normal oxygen, hypoxic conditions (1% O2) or 5 μM DFO for 24 h. Then, cells were treated with 10B-boronophenylalanine (BPA) for 2 h and boron accumulation in cells was evaluated. To clarify the relationship between HIF-1α and L-type amino acid transporter 1 (LAT1), gene expression was evaluated by a using HIF-1α gene knockdown technique. Finally, to improve attenuation of the effects of BNCT in hypoxic cells, BNCT was combined with YC-1. Boron uptake was continuously suppressed up to 2 h after administration of BPA by 5 μM DFO treatment. In cells treated with 5 μM DFO, LAT1 expression was restored in HIF-1α-knocked down samples in all cell lines, revealing that HIF-1α suppresses LAT1 expression in hypoxic cells. From the results of the surviving fraction after BNCT combined with YC-1, treatment with YC-1 sensitized the antitumor effects of BNCT in cells cultured in hypoxia.

Functionalized mesoporous silica nanoparticles for innovative boron-neutron capture therapy of resistant cancers

2018 ◽  
Author(s):  
Guillaume Vares ◽  
Vincent Jallet ◽  
Yoshitaka Matsumoto ◽  
Cedric Rentier ◽  
Kentaro Takayama ◽  
...  
Keyword(s):  
Mesoporous Silica ◽  
Silica Nanoparticles ◽  
Boron Neutron Capture Therapy ◽  
Neutron Capture ◽  
Mesoporous Silica Nanoparticles ◽  
Alpha Particles ◽  
Neutron Capture Therapy ◽  
Boron Neutron Capture

AbstractTreatment resistance, relapse and metastasis remain critical issues in some challenging cancers, such as chondrosarcomas. Boron-neutron Capture Therapy (BNCT) is a targeted radiation therapy modality that relies on the ability of boron atoms to capture low energy neutrons, yielding high linear energy transfer alpha particles. We have developed an innovative boron-delivery system for BNCT, composed of multifunctional fluorescent mesoporous silica nanoparticles (B-MSNs), grafted with an activatable cell penetrating peptide (ACPP) for improved penetration in tumors and with Gadolinium for magnetic resonance imaging (MRI)in vivo. Chondrosarcoma cells were exposedin vitroto an epithermal neutron beam after B-MSNs administration. BNCT beam exposure successfully induced DNA damage and cell death, including in radio-resistant ALDH+ cancer stem cells (CSCs), suggesting that BNCT using this system might be a suitable treatment modality for chondrosarcoma or other hard-to-treat cancers.

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