Terahertz (THz) radiation has gained attention due to technological advancements, but its biological effects remain unclear. We investigated the impact of 2.3 THz radiation on SK-MEL-28 cells using metabolomic and gene network analysis. Forty metabolites, primarily related to purine, pyrimidine synthesis and breakdown pathways, were significantly altered post-irradiation. Lipids, such as ceramides and phosphatidylcholines, were also affected. Gene network reconstruction and analysis identified key regulators of the enzymes involved in biosynthesis and degradation of significantly altered metabolites. Mitochondrial membrane components, such as the respiratory chain complex, the proton-transporting ATP synthase complex, and components of lipid rafts reacted to THz radiation. We propose that THz radiation induces reversible disruption of the lipid raft macromolecular structure, thereby altering mitochondrial molecule transport while maintaining protein integrity, which explains the high cell survival rate. Our findings enhance the understanding of THz biological effects and emphasize the role of membrane components in the cellular response to THz radiation.

Targeted therapeutic delivery to specific regions of the central nervous system (CNS) is a promising approach for treating localized pathologies such as neuropathic pain or viral infections. The systemic administration of drugs is often inefficient, as it distributes medication throughout the body, including non-targeted CNS areas, rather than concentrating it in the affected neural tissues. Leveraging axonal transport for targeted drug delivery could enable precise therapeutic interventions, such as antiviral, antineuropathic, or regenerative treatments, selectively directed to specific ganglia or CNS cells. In this study, we developed a novel strategy using magnetoelectric (ME) nanotransducers based on the core-shell MnFe2O4@Ba0.85Ca0.15Zr0.1Ti0.9O3 nanoparticles (MFO@BCZT NPs), which exhibit an exceptionally high ME response (12.2 × 105 mV·cm-1·Oe-1), to facilitated axonal transport of cargoes from the nasal cavity to the brain by a low-intensity alternating magnetic field (0-50 Hz, 0-30 mT). Firstly, in vitro experiments demonstrated that MFO@BCZT NPs efficiently activated voltage-gated calcium channels in primary neurons under safe magnetic stimulation. Ex vivo studies further confirmed enhanced cellular uptake of MFO@BCZT NPs and their ability for effective wireless stimulation of mouse hippocampal slices. Finally, in vivo experiments revealed significant ME-mediated improvement of axonal transport of BSA-Cy7 from nasal cavity into the mouse brain using MFO@BCZT NPs. This study establishes a non-invasive ME nanoplatform for spatiotemporally controlled neuronal logistics, offering a transformative approach for targeted therapeutic delivery to CNS.

Derivatives of natural amino acids are selectively absorbed by many types of tumour cells. This makes the use of amino acids, especially polyfunctional ones, attractive as a basis in the design of low-toxicity agents for targeted boron delivery for boron neutron capture therapy (BNCT) of tumours. We synthesized a series of new (S)-ornithine and (S)-lysine derivatives containing a 7,8-dicarba-nido-undecaborane (nido-carborane) residue attached to the amino group in the side chain or alpha position. The MTT assay demonstrated moderate cytotoxicity of the lysine and ornithine derivatives containing a nido-carborane residue in the side chain. It has been found that sodium salt of Nε-(nido-carboran-7-yl)acetyl-(S)-lysine is capable of accumulation by MDA-MB-231 (human breast carcinoma) and SK-Mel 28 (human melanoma) cell lines, providing a boron concentration of up to 0.67 µg/106 cells in in vitro experiments. This (S)-lysine derivative containing a nido-carborane residue in the side chain can be considered as a promising compound for in-depth study in vivo experiments aimed at designing an efficient boron delivery agent for BNCT.

We studied cytotoxicity and accumulation of boron and lithium by cultured human fibroblasts and human and mouse skin melanoma cell cultures. The cytotoxicity of boron and lithium drugs was assessed by MTT tests in the boron and lithium concentration range of 10-640 μg/ml. Cell viability was significantly reduced after incubation with boron and lithium at concentrations >160 μg/ml. To assess accumulation of boron and lithium, the concentration of elements was measured using inductively coupled plasma atomic emission spectrometry. Melanoma cells more intensively accumulated lithium in comparison with boron. The results indicate the possibility of safe application of lithium salts in concentrations minimally required for successful neutron capture therapy.

Metronidazole is a prospective hyperpolarized MRI contrast agent with potential hypoxia sensing utility for applications in cancer, stroke, neurodegenerative diseases, etc. We demonstrate a pilot procedure for production of ∼30 mM hyperpolarized [15N3]metronidazole in aqueous media by using a phase-separated SABRE-SHEATH hyperpolarization method, with nitrogen-15 polarization exceeding 2.2% on all three 15N sites achieved in less than 2 min. The 15N polarization T1 of ∼12 min is reported for the 15NO2 group at the clinically relevant field of 1.4 T in the aqueous phase, demonstrating a remarkably long lifetime of the hyperpolarized state. The produced aqueous solution of [15N3]metronidazole that contained only ∼100 μM of residual Ir was deemed biocompatible via validation through the MTT colorimetric test for assessing cell metabolic activity using human embryotic kidney HEK293T cells. This low-cost and ultrafast hyperpolarization procedure represents a major advance for the production of a biocompatible HP [15N3]metronidazole (and potentially other hyperpolarized drugs) formulation for MRI sensing applications.

Boron neutron capture therapy (BNCT) is one of the most appealing radiotherapy modalities, whose localization can be further improved by the employment of boron-containing nanoformulations, but the fabrication of biologically friendly, water-dispersible nanoparticles (NPs) with high boron content and favorable physicochemical characteristics still presents a great challenge. Here, we explore the use of elemental boron (B) NPs (BNPs) fabricated using the methods of pulsed laser ablation in liquids as sensitizers of BNCT. Depending on the conditions of laser-ablative synthesis, the used NPs were amorphous (a-BNPs) or partially crystallized (pc-BNPs) with a mean size of 20 nm or 50 nm, respectively. Both types of BNPs were functionalized with polyethylene glycol polymer to improve colloidal stability and biocompatibility. The NPs did not initiate any toxicity effects up to concentrations of 500 µg/mL, based on the results of MTT and clonogenic assay tests. The cells with BNPs incubated at a 10B concentration of 40 µg/mL were then irradiated with a thermal neutron beam for 30 min. We found that the presence of BNPs led to a radical enhancement in cancer cell death, namely a drop in colony forming capacity of SW-620 cells down to 12.6% and 1.6% for a-BNPs and pc-BNPs, respectively, while the relevant colony-forming capacity for U87 cells dropped down to 17%. The effect of cell irradiation by neutron beam uniquely was negligible under these conditions. Finally, to estimate the dose and regimes of irradiation for future BNCT in vivo tests, we studied the biodistribution of boron under intratumoral administration of BNPs in immunodeficient SCID mice and recorded excellent retention of boron in tumors. The obtained data unambiguously evidenced the effect of a neutron therapy enhancement, which can be attributed to efficient BNP-mediated generation of α-particles.

Nanoparticles (NPs) can be transported via the nose-to-brain (N2B) route. Nonetheless, quantitative data on their spatiotemporal dynamics and regulation of the N2B transport are largely lacking. We surveyed metal oxide/hydroxide NPs as magnetic resonance imaging (MRI) contrasts for quantitative N2B tracking. NPs containing divalent transition metals were the only ones capable of N2B transmission. Using T-1-weighted (T1W) MRI, we showed that Mn3O4-NPs were readily engulfed by olfactory receptor neurons (ORNs) without disrupting olfactory sensing, and we mapped their N2B trajectory. Within neurons, the Mn3O4-NPs were localized to the cytosol, mitochondria, and vesicles, and moved at mixed fast and slow axonal transport velocities intra- and extra-vesicularly through ORNs. The NPs' axonal transport is dependent on neuronal activity and microtubule integrity. The Mn3O4-NPs were trans-synaptically transmitted through at least four synapses across the olfactory tract. Trans-synaptic transmission of the NPs was dependent on N-type Ca2+ channels and NMDA receptors but blocked by GABA(B) receptor activation. A five-parameter Weibull signal increase/decrease model fitted to the T1W MRI data allowed for estimating kinetic parameters of Mn3O4-NP accumulation/elimination. Absolute and relative accumulation rates, but not elimination, correlated negatively with the number of synapses from ORNs, indicating a coupling of the NPs' N2B transport with spontaneous neuronal activity. Accordingly, olfactory stimuli (2,5-dimethylpyrazine and acetophenone) significantly modulated and rerouted the Mn3O4-NP N2B transport odor specifically. Finally, the NPs' trans-synaptic transmission was impaired by aging and the onset of Parkinson's disease. These data suggest new approaches to diagnostics, functional neuroimaging, and controlling N2B drug delivery.

Boron neutron capture therapy is considered a promising method for the treatment of malignant tumors of the head and neck. It is believed that to increase the effectiveness of this type of therapy, the use of large doses of boron is required, which may entail damaging effects on healthy tissue. One of the substances used in the clinical practice of boron neutron capture therapy is sodium boroncaptate Na 2 B 12 H 11 SH (BSH), enriched with the 10B boron isotope. The purpose of the study was to study the structural reactions of the myocardium and liver of CD-1 mice after administration of BSH. A light-optical and polarization-microscopic study of the myocardium and liver of male CD-1 mice (n=56) was carried out after injection of a boron-containing substance in doses of 100 and 1000 mg/kg, once, intraperitoneally. Assessment of structural changes in the myocardium and liver was carried out 1, 3 and 7 days after BSH administration. A single injection of BSH at a dose of 100 mg/kg did not lead to the death of animals, whereas 3 hours after the injection of BSH at a dose of 1000 mg/kg, 1 animal died. The body weight of the animals changed slightly during the experiment. Analysis of heart weight showed a decrease in this indicator on days 3 and 7 compared with indicators in the same groups on day 1 of the experiment. When analyzing the dynamics of changes in liver mass, no significant changes were revealed during the experiment. The main structural changes in the myocardium included lytic and contractural damage to cardiomyocytes, hemodynamic disturbances in the form of pronounced venous and capillary congestion. Liver damage was manifested in dystrophic changes in hepatocytes, the appearance after 3 days of monocellular necrosis of hepatocytes and pericentral mononuclear infiltrates. The data obtained indicate that the used doses of BSH 100 and 1000 mg/kg with a single injection cause structural changes in the myocardium and liver of varying severity, which persist for 7 days of observation.

Orthotopic transplantation of glioblastoma cells in the brain of laboratory mice is a common animal model for studying brain tumors. It was shown that 1H magnetic resonance spectroscopy (MRS) enables monitoring of the tumor’s occurrence and its development during therapy based on the ratio of several metabolites. However, in studying new approaches to the therapy of glioblastoma in the model of orthotopic xenotransplantation of glioma cells into the brain of mice, it is necessary to understand which metabolites are produced by a growing tumor and which are the result of tumor cells injection along the modeling of the pathology. Currently, there are no data on the dynamic metabolic processes in the brain that occur after the introduction of glioblastoma cells into the brain of mice. In addition, there is a lack of data on the delayed effects of invasive brain damage. Therefore, this study investigates the long-term dyna mics of the neurometabolic profile, assessed using 1H MRS, after intracranial injection of a culture medium used in orthotopic modeling of glioma in mice. Levels of N-acetylaspartate, N-acetylaspartylglutamic acid, myoinositol, taurine, glutathione, the sum of glycerophosphocholine and phosphocholine, glutamic acid (Glu), glutamine (Gln), and gamma aminobutyric acid (GABA) indicate patterns of neurometabolites in the early stage after intracranial injection similar to brain trauma ones. Most of the metabolites, with the exception of Gln, Glu and GABA, returned to their original values on day 28 after injection. A progressive increase in the Glu/Gln and Glu/GABA ratio up to 28 days after surgery potentially indicates an impaired turnover of these metabolites or increased neurotransmission. Thus, the data indicate that the recovery processes are largely completed on day 28 after the traumatic event in the brain tissue, leaving open the question of the neurotransmitter system impairment. Consequently, when using animal models of human glioma, researchers should clearly distinguish between which changes in neurometabolites are a response to the injection of cancer cells into the brain, and which processes may indicate the early development of a brain tumor. It is important to keep this in mind when modeling human glioblastoma in mice and monitoring new treatments. In addition, these results may be important in the development of approaches for non-invasive diagnostics of traumatic brain injury as well as recovery and rehabilitation processes of patients after certain brain surgeries.

Further studies on the mechanism of intracellular induction of active oxygen species and selective oncolysis with metal oxide nanoparticles (NPs), as well as the discussion of alternative mechanisms of the NPs impact on tumor cells, are needed to introduce nanotechnologies into antitumor therapy. The paper concerns the inhibition of oxidation processes in tumor cells under the action of manganese oxide-based NPs (size 10–60 nm) as the mechanism of a tumor cell death. When manganese (II) hydroxide-based NPs enter the cells, they are oxidized with oxygen to Mn4+ compounds; the oxidation processes being blocked in the tumor cells. Hence, the MnO NPs cytotoxicity can be due to the possible direct reduction of O2 in the presence of manganese compounds in the cells.

Boron neutron capture therapy is a perspective selective technology for the destruction of cancer cells, while the use of lithium instead of boron may represent a new and promising vector for the development of neutron capture therapy (NCT). The aim of the study was a comparative assessment of the cytotoxicity of various lithium salts, as well as an analysis of the accumulation of lithium in tumor cells in vitro to determine the possibility of using lithium in NCT. The cytotoxicity of lithium salts was determined using MTT-test and colony forming assay on human fibroblasts BJ-5ta, human skin melanoma SK-Mel-28, and mouse skin melanoma B16 cell lines. An assessment of lithium concentration in cells was performed using inductively coupled plasma atomic emission spectrometry. Our results showed that three different lithium salts at a concentration of 40 μg/ml are not toxic for both tumor and normal cells. The highest uptake values were obtained on murine melanoma B16 cells when exposed to lithium carbonate (0.8 μg/106 cells); however, human melanoma SK-Mel-28 cells effectively accumulated both lithium carbonate and lithium citrate (about 0.46 μg/106 cells for two salts). Thus, our results demonstrate a range of non-toxic doses of lithium salts and a high uptake of lithium by tumor cells, which indicates the possibility to use the lithium in NCT.

The novel conjugates of cholesterol with cobalt – bis(dicarbollide) were synthesized by the ring-opening reactions of the cyclic oxonium derivatives of [3,3′-Co(C2B9H11)2]– with the OH group of cholesterol 2-hydroxyethyl ether. The compounds obtained were tested for toxicity to glioblastoma U-87 MG cells and human embryo fibroblasts FECH-15 cells

In this research, an experimental U87 glioblastoma small animal model was studied. The association between glioblastoma stages and the spectral patterns of mouse blood serum measured in the terahertz range was analyzed by terahertz time-domain spectroscopy (THz-TDS) and machine learning. The THz spectra preprocessing included (i) smoothing using the Savitsky–Golay filter, (ii) outlier removing using isolation forest (IF), and (iii) Z-score normalization. The sequential informative feature-selection approach was developed using a combination of principal component analysis (PCA) and a support vector machine (SVM) model. The predictive data model was created using SVM with a linear kernel. This model was tested using k-fold cross-validation. Achieved prediction accuracy, sensitivity, specificity were over 90%. Also, a relation was established between tumor size and the THz spectral profile of blood serum samples. Thereby, the possibility of detecting glioma stages using blood serum spectral patterns in the terahertz range was demonstrated.

The design of highly selective low-toxic, low-molecular weight agents for boron delivery to tumour cells is of decisive importance for the development of boron neutron capture therapy (BNCT), a modern efficient combined method for cancer treatment. In this work, we developed a simple method for the preparation of new closo- and nido-carborane-containing folic acid bis-amides containing 18–20 boron atoms per molecule. Folic acid derivatives containing nido-carborane residues were characterised by high water solubility, low cytotoxicity, and demonstrated a good ability to deliver boron to tumour cells in in vitro experiments (up to 7.0 µg B/106 cells in the case of U87 MG human glioblastoma cells). The results obtained demonstrate the high potential of folic acid–nido-carborane conjugates as boron delivery agents to tumour cells for application in BNCT.

A promising area of oncotherapy is the use of nanomaterials for diagnostics and imaging, as well as for delivering drugs and direct effect agents to tumour cells. We used earlier manganese oxide nanoparticles (NP MnO) as magnetic resonance imaging agents for visualisation and suppression of in vitro and in vivo growth of human glioblastoma cells. The present study was to demonstrate the selective antitumor effect of NP MnO against human tumour cells of different tissue origins, in particular, cells SW620, human colorectal adenocarcinoma. It was shown that NP MnO can inhibit selectively in vitro growth of SW620 cells; the index of selective cytotoxicity against human colorectal adenocarcinoma cells was 20. The range of optimal NP MnO doses was determined using subcutaneous introduction of the nanoparticles to SCID mice; the doses no more than 0.96 mgMn kg −1 had practically no local toxic effect in the animals. The subcutaneous administration of NP MnO in the specified dose range inhibited the growth of SW620 xenografts in SCID mice and led to an increase in their life expectancy. With administered NP MnO in doses of 0.32 and 0.96 mgMn kg −1 , the index of inhibition of tumour growth for 21 days from the beginning of the introduction of nanoparticles was 43.0% and 69.8%, respectively. NP MnO seem promising for developing nanotheranostics agents for the visualisation and treatment of human tumours of different tissue origins.

According to the World Health Organization, colorectal cancer is one of the three leading causes of death among other tumors. Boron neutron capture therapy (BNCT) is a promising method for the treatment of oncological diseases. It is an experimental method of radiation therapy which is based on the capture reaction of a thermal neutron by an isotope B-10 and results in the B-10(n, alpha)Li-7 fission reaction. The high linear energy transfer from alpha particle and Li-7 nucleus has a short path length, thus the energy released is limited to the size of one cell. Previously, BNCT was actively used to treat patients with glioblastoma, melanoma, head and neck cancer, and other malignant neoplasms of various localization. The aim of this work is to determine the safe concentrations of boronphenylalanine (BPA) and sodium borocaptate (BSH) drugs for the SW-620 cell line and to assess the B-10 biodistribution after administration of these compaunds to immunodeficient SCID mice with heterotopic SW-620 xenografts. To evaluate the possibility of using BNCT as a therapy for patients with colorectal cancer, we carried out preliminary in vitro and in vivo studies on the model of human colorectal adenocarcinoma SW-620. Firstly, the cytotoxicity of boron compounds BPA and BSH at B-10 concentrations of 10-1280 mu g/ml was investigated using MTT test. All animal experiments were conducted in accordance with the principles of humane treatment of animals in compliance with the directive of the European Community (86/609 / EEC) and correspond to the principles of the Guide for the Care and Use of Laboratory Animals (NIH USA, No 85-23, rev. 1985). To determine the toxicity of BPA and BSH in standard dosages, drugs were intravenously injected into the retroorbital sinus: BPA at a concentration of 350 mg/kg and BSH at 100 mg/kg. The control group of animals were injected intravenously with sodium chloride 0.9%. After 2 months of observation planned euthanasia was done, organs (kidneys, liver, lungs, brain and heart) were sampled for pathomorphological study. Biodistribution of B-10 in the tumor and organs of interest was performed on mice with SW-620 heterotopic xenograft. Boron containing drugs were injected at the dosages described earlier intravenously into the retroorbital sinus. Euthanasia was performed 1, 2, 3, and 4 hours after injection, tumor tissue, blood, brain, liver and kidneys were sampled. The boron concentration was analyzed by inductively coupled plasma atomic emission spectrometry (ICP AES). As a result of the MTT test, we revealed that incubation of SW-620 cells with BPA and BSH for 24 and 48 hours at B-10 concentrations of 10-320 mu g/ml had no cytotoxic effect. When incubated for 48 hours with BPA at a concentration of 320 mu g/ml, survival rate did not differ significantly from control. The maximum safe concentration for BSH can also be considered 320 mu g/ml of B-10, since the cell survival in the experimental groups was 96 and 95.5% for 24 and 48 hours of incubation with the drug, respectively. The first significant cytotoxic effects were noted during incubation with both boron-containing drugs at a B-10 concentration of 640 mu g/ml. For the BPA group, the percentage of survived cells was 65 (incubation for 24 hours) and 51 (48 hours), BSH had less cytotoxic effect: cell survival decreased to 87% and 80.5% at points 24 and 48 hours, respectively (See Fig. 1). Intravenous administration of BPA at a concentration of 350 mg/kg and BSH at a concentration of 100 mg/kg to SCID mice turned out to be safe: no pathological reactions were detected within 2 months of observation, all animals were alive. According to the pathomorphological study, no macroscopic and structural changes in the organs were found (See Fig. 2). The biodistribution of B-10 was assessed in SCID mice with subcutaneous xenografts SW-620 after intravenous administration of boron drugs at standard concentrations. As a result of the analysis, we found out that after intravenous administration of BPA at a safe dosage, the maximum concentration of B-10 in the tumor was recorded at the time points of 1 and 2 hours (8.0 and 8.7 mu g/g, respectively). In this case, the concentration ratio of B-10 in the tumor and blood samples was determined as 0.6 for the 1 hour point and 1.7 for the 2 hour point. We also demonstrated that the kidneys were the organ with the highest boron accumulation throughout the experiment (See Fig. 3). Thus, the time point of 2 hours can be considered potentially the most suitable for BNCT, but the concentration of boron in the tumor tissue is not sufficient. For BSH the maximum concentration was recorded at the time point of 1 hour (5.7 mu g/g). The liver, kidneys and blood contained the highest concentration of B-10 (See Fig. 4). Thus, apparently, further investigations on increasing the dose of the drugs and choosing different ways of boron agents administration can increase the accumulation of B-10 by the tumor and reduce its concentration in the surrounding tissues and blood. The use of additional drugs that improve the penetration of boron into the tumor may also be effective and should be taken into account.

48-56 ОЦЕНКА ЭФФЕКТИВНОСТИ БОР-НЕЙТРОНОЗАХВАТНОЙ ТЕРАПИИ НА ГЕТЕРОТОПИЧЕСКОЙ МОДЕЛИ ГЛИОБЛАСТОМЫ U87 У ИММУНОДЕФИЦИТНЫХ МЫШЕЙ ЛИНИИ SCID Кривошапкин А.Л. 1 , Каныгин В.В. 1 , Касатова А.И. 2 , Сёмин П.А. 3 , Кичигин А.И. 2 , Разумов И.А. 4 , Соловьева О.И. 4 , Завьялов Е

Introduction. Boron neutron capture therapy (bnct) is a promising method for treating tumors, in particular, infiltrative malignant tumors, due to the selective destruction of tumor cells without damaging the surrounding normal tissues. This type of therapy is based on nuclear reaction of neutron capture by stable 10b isotope. For the successful implementation of bnct, boron delivery drugs that must be selectively accumulated in malignant cells in a sufficient amount, and a neutron source with the energy required for the neutron capture reaction are needed. At the budker institute of nuclear physics, the accelerator-based neutron source was designed with flux parameters allowing studies on bnct to be conducted. Objective: to assess the effect of bnct on tumor and normal cell lines using borphenylalanine (bpa), borcaptate (bsh) and liposomal borcaptat as boron delivery drugs. Materials and methods. Human cell cultures: glioblastoma (u87), colorectal human adenocarcinoma (sw-620), human melanoma (sk-mel28) and primary embryonic cell lines were irradiated with a neutron flux at the presence of bpa, bsh and liposomal bsh with a concentration of 10b 40 μg/ml. The short-term cytotoxic effect of irradiation was evaluated using trypan blue. Cell survival 96 hours after irradiation was determined using mtt test, and survival fraction was evaluated using the clonogenic test. Results. Early cytotoxic effects of irradiation were not observed for all 4 cell lines. According to mtt and clonogenic tests, the most pronounced effect of bnct was noticed for sw-620 and u87 lines, regardless of boron delivery drug used. For sk-mel28 line, the best effect was achieved after irradiation with liposomal borocaptate. For the primary transplanted embryonic line, high toxicity was revealed when bnct was performed with borphenylalanine and borcaptate. Conclusion. The data obtained indicate that the accelerator-based bnct using boron delivery drugs, such as borphenylalanine, borcaptate and liposomal borcaptat, has a positive effect on tumor lines of glioblastoma, colorectal adenocarcinoma and melanoma.

(1) Background: Developments in accelerator-based neutron sources moved boron neutron capture therapy (BNCT) to the next phase, where new neutron radiation parameters had to be studied for the treatment of cancers, including brain tumors. We aimed to further improve accelerator-BNCT efficacy by optimizing dosimetry control, beam parameters, and combinations of boronophenylalanine (BPA) and sodium borocaptate (BSH) administration in U87MG xenograft-bearing immunodeficient mice with two different tumor locations. (2) Methods: The study included two sets of experiments. In Experiment #1, BPA only and single or double irradiation in higher doses were used, while, in Experiment #2, BPA and BSH combinations and single or double irradiation with dosage adjustment were analyzed. Mice without treatment or irradiation after BPA or BPA+BSH injection were used as controls. (3) Results: Irradiation parameter adjustment and BPA and BSH combination led to 80–83% tumor-growth inhibition index scores, irradiation:BNCT ratios of 1:2, and increases in animal life expectancy from 9 to 107 days. (4) Conclusions: Adjustments in dosimetry control, calculation of irradiation doses, and combined use of two 10B compounds allowed for BNCT optimization that will be useful in the development of clinical-trial protocols for accelerator-based BNCT.

Introduction. Boron neutron capture therapy (bnct) is a promising method for treating tumors, in particular, infiltrative malignant tumors, due to the selective destruction of tumor cells without damaging the surrounding normal tissues. This type of therapy is based on nuclear reaction of neutron capture by stable 10b isotope. For the successful implementation of bnct, boron delivery drugs that must be selectively accumulated in malignant cells in a sufficient amount, and a neutron source with the energy required for the neutron capture reaction are needed. At the budker institute of nuclear physics, the accelerator-based neutron source was designed with flux parameters allowing studies on bnct to be conducted.Objective: to assess the effect of bnct on tumor and normal cell lines using borphenylalanine (bpa), borcaptate (bsh) and liposomal borcaptat as boron delivery drugs.Materials and methods. Human cell cultures: glioblastoma (u87), colorectal human adenocarcinoma (sw-620), human melanoma (sk-mel28) and primary embryonic cell lines were irradiated with a neutron flux at the presence of bpa, bsh and liposomal bsh with a concentration of 10b 40 μg/ml. The short-term cytotoxic effect of irradiation was evaluated using trypan blue. Cell survival 96 hours after irradiation was determined using mtt test, and survival fraction was evaluated using the clonogenic test.Results. Early cytotoxic effects of irradiation were not observed for all 4 cell lines. According to mtt and clonogenic tests, the most pronounced effect of bnct was noticed for sw-620 and u87 lines, regardless of boron delivery drug used. For sk-mel28 line, the best effect was achieved after irradiation with liposomal borocaptate. For the primary transplanted embryonic line, high toxicity was revealed when bnct was performed with borphenylalanine and borcaptate.Conclusion. The data obtained indicate that the accelerator-based bnct using boron delivery drugs, such as borphenylalanine, borcaptate and liposomal borcaptat, has a positive effect on tumor lines of glioblastoma, colorectal adenocarcinoma and melanoma.