Lithium salts cytotoxicity and accumulation in melanoma cells in vitro.

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.

Laser-Synthesized Elemental Boron Nanoparticles for Efficient Boron Neutron Capture Therapy.

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.

Nanocomposite Materials Based on Polylactide and Gold Complex Compounds for Absorbed Dose Diagnostics in BNCT.

In this study, approaches to the synthesis of complex compound of gold with cysteine [AuCys]n for measuring absorbed dose in boron neutron capture therapy (BNCT) were developed. The dependence of the complex particle size on pH were established. Nanocomposite materials based on polylactide containing [AuCys]n particles with an average size of about 20 nm were obtained using the crazing mechanism. The structure of obtained materials was studied by electron microscopy. The release kinetics of [AuCys]n from polymer matrix were investigated. Release of [AuCys]n from the volume of the polymeric matrix had a delayed start-this process began only after 24 h and was characterized by an effective rate constant of 1 µg/h from a 20 mg composite sample. At the same time, in vitro studies showed that the concentration of 6.25 µg/mL was reliably safe and did not reduce the survival of U251 and SW-620 cells.

Magnetic Soft Robot for Minimally Invasive Urethral Catheter Biofilm Eradication.

Catheter-related biofilm infection remains the main problem for millions of people annually, affecting morbidity, mortality, and quality of life. Despite the recent advances in the prevention of biofilm formation, alternative methods for biofilm prevention or eradication still should be found to avoid traumatic and expensive removal or catheter replacement. Soft magnetic robots have drawn significant interest in favor of remote control, fast response, and wide space for design. In this work, we demonstrated magnetic soft robots as a minimally invasive, safe, and effective approach to eliminate biofilm from urethral catheters (20 Fr or 5.1 mm in diameter). Seven designs of the robot were fabricated (size 4.5 × 15 mm), characterized, and tested in the presence of a rotating magnetic field. As a proof-of-concept, we demonstrated the superior efficiency of biofilm removal on the model of a urethral catheter using a magnetic robot, reaching full eradication for the octagram-shaped robot (velocity 2.88 ± 0.6 mm/s) at a 15 Hz frequency and a 10 mT amplitude. These findings are helpful for the treatment of biofilm-associated catheter contamination, which allows an increase in the catheter wearing time without frequent replacement and treatment of catheter-associated infections.

Preparation, phase stability, and magnetization behavior of high entropy hexaferrites.

The polycrystalline SrFe12O19 samples deeply substituted up to at.67% by Al3+, Ga3+, In3+, Co3+, and Cr3+ cations with a high configurational mixing entropy were prepared by solid-phase synthesis. Phase purity and unit cell parameters were obtained from XRD and analyzed versus the average ionic radius of the iron sublattice. The crystallite size varied around ∼4.5 µm. A comprehensive study of the magnetization was realized in various fields and temperatures. The saturation magnetization was calculated using the Law of Approach to Saturation. The accompanying magnetic parameters were determined. The magnetic crystallographic anisotropy coefficient and the anisotropy field were calculated. All investigated magnetization curves turned out to be nonmonotonic. The magnetic ordering and freezing temperatures were extracted from the ZFC and FC curves. The average size of magnetic clusters varied around ∼350 nm. The high values of the configurational mixing entropy and the phenomenon of magnetic dilution were taken into account.

A single coned Poly-Biz moderator designed for animal irradiation in boron neutron capture therapy.

BNCT is considered to be a promising method for the treatment of malignant tumors, which ensures the selective destruction of malignant tumor cells by accumulating non-radioactive atomic boron-10 nuclei in them and subsequent irradiation with neutrons. As a result of the absorption of a neutron by boron, a nuclear reaction occurs with the release of energy in a cell containing boron, which leads to its death. To date, two drugs for targeted delivery of boron, boronophenylalanine and sodium borocaptate, have been developed, which ensures selective accumulation of boron in a number of tumors, and a number of charged particle accelerators with neutron-generating targets and with neutron beam shaping assemblies have been developed providing the quality of the neutron beam required for therapy. The paper presents a critical analysis of the methods used to form a therapeutic neutron beam and proposes a new concept of a neutron beam shaping assembly, supported by the results of numerical simulation validated by in-phantom measurements.

Gadolinium Neutron Capture Therapy for Cats and Dogs with Spontaneous Tumors Using Gd-DTPA.

We conducted a clinical veterinary study on neutron capture therapy (NCT) at a neutron-producing accelerator with seven incurable pets with spontaneous tumors and gadolinium as a neutron capture agent (gadolinium neutron capture therapy, or GdNCT). Gadolinium-containing dimeglumine gadopentetate, or Gd-DTPA (Magnevist®, 0.6 mL/kg b.w.), was used. We observed mild and reversible toxicity related to the treatment. However, no significant tumor regression in response to the treatment was observed. In most cases, there was continued tumor growth. Overall clinical improvement after treatment was only temporary. The use of Gd-DTPA for NCT had no significant effects on the life expectancy and quality of life of animals with spontaneous tumors. Further experiments using more advanced gadolinium compounds are needed to improve the effect of GdNCT so that it can become an alternative to boron neutron capture therapy. Such studies are also necessary for further NCT implementation in clinical practice as well as in veterinary medicine.

Design of the New Closo-Dodecarborate-Containing Gemcitabine Analogue for the Albumin-Based Theranostics Composition.

Combination therapy is becoming an increasingly important treatment strategy because multi-drugs can maximize therapeutic effect and overcome potential mechanisms of drug resistance. A new albumin-based theranostic containing gemcitabine closo-dodecaborate analogue has been developed for combining boron neutron capture therapy (BNCT) and chemotheraphy. An exo-heterocyclic amino group of gemcitabine was used to introduce closo-dodecaborate, and a 5'-hydroxy group was used to tether maleimide moiety through an acid-labile phosphamide linker. The N-trifluoroacylated homocysteine thiolactone was used to attach the gemcitabine analogue to human serum albumin (HSA) bearing Cy5 or Cy7 fluorescent dyes. The half-maximal inhibitory concentration (IC50) of the designed theranostic relative to T98G cells was 0.47 mM with the correlation coefficient R = 0.82. BNCT experiments resulted in a decrease in the viability of T98G cells, and the survival fraction was ≈ 0.4.

Study of Lithium Biodistribution and Nephrotoxicity in Skin Melanoma Mice Model: The First Step towards Implementing Lithium Neutron Capture Therapy.

Boron neutron capture therapy (BNCT) is one of the promising treatment methods for malignant melanoma. The main issue of this technology is the insufficient selectivity of 10B accumulation in tumor cells. As a result of the neutron absorption by boron, an 84% energy release occurred within the cell by the nuclear reaction 10B (n, α)7Li, which lead to tumor cell death. The use of lithium instead of boron brings a new unique opportunity-local 100% energy release-since all products of the 6Li (n, α)3H reaction have high linear energy transfer characteristics. The aim of this study was to determine the concentrations of Li in the tumor, skin, blood, brain and kidney in experimental animals with B16 melanoma and to analyze the potential Li toxicity after lithium carbonate administration at single doses of 300 and 400 mg/kg. Lithium carbonate was chosen since there is a long-term experience of its use in clinical practice for the treatment of psychiatric disorders. The inductively coupled plasma atomic emission spectrometry was used to evaluate Li concentrations in tissue samples. The accumulation efficiency of Li in the tumor was the highest at a time point of 30 min (22.4 µg/g; at a dose of 400 mg/kg). Despite the high lithium accumulation in the kidneys, the pathological changes in kidney tissues were not found. Thus, lithium may actually be used for the Li-NCT development and future studies can be conducted using 6Li and following irradiation of tumor cells using the schemes of lithium administration tested in this work.

Reprogrammable Soft Swimmers for Minimally Invasive Thrombus Extraction.

Thrombosis-related diseases are the primary cause of death in the world. Despite recent advances in thrombosis treatment methods, their invasive nature remains a crucial factor, which leads to considerable deadly consequences. Soft magnetic robots are attracting widespread interest due to their fast response, remote actuation, and shape reprogrammability and can potentially avoid the side effects of conventional approaches. This paper outlines a new approach to the thrombosis treatment via reprogrammable magnetic soft robots that penetrate, hook, and extract the plasma clots in a vein-mimicking system under applied rotating magnetic fields. We present shape-switching bioinspired soft swimmers, capable of locomotion by different mechanisms in vein-mimicking flow conditions and whose swimming efficiency is similar to animals. Further, we demonstrate the potential of a developed robot for minimally invasive thromboextraction with and without fibrinolytic usage, including hooking the plasma clot for 3.1 ± 1.1 min and extracting it from the vein-mimicking system under the applied magnetic fields. We consider an interesting solution for thrombosis treatment to avoid substantial drawbacks of the existing methods.

Creation and Magnetic Study of Ferrites with Magnetoplumbite Structure Multisubstituted by Al3+, Cr3+, Ga3+, and In3+ Cations.

Multisubstituted barium ferrites with a magnetoplumbite structure were obtained by the method of solid-phase reactions with ferritization and pre-firing. Three-charged, mainly diamagnetic cations Al3+, Cr3+, Ga3+, and In3+ were chosen as substituents for the Fe3+ iron cations, the proportion of which in solid solutions did not exceed 50%. The values of the configurational mixing entropy were calculated for all the compositions. A slight deviation of the chemical composition of the obtained solid solutions from the nominal value was established by the energy-dispersive X-ray spectroscopy method. The phase purity and values of the unit cell parameters were refined from X-ray scattering data using full-profile analysis in the Rietveld method. A non-monotonic behavior of the unit cell parameters as a function of the B-sub-lattice average ionic radius of the magnetoplumbite structure was found. A minimum unit cell volume of ~667.15 Å3 was found for the composition BaFe6.11Al1.56Cr2.17Ga2.16O19 with a B-sub-lattice average ionic radius of ~7.449 Å. The average crystallite size varied within 5.5-6.5 µm. The temperature and field dependencies of the magnetization have been measured. The values of the saturation magnetization, residual magnetization, hysteresis loop squareness, and coercivity at 50 K and 300 K were extracted from the experimental data. Using the Law of Approach to Saturation, the magnetic crystallographic anisotropy coefficient and anisotropy field were calculated. Multisubstitution leads to a significant decrease in such magnetic parameters as the magnetic ordering temperature and spontaneous magnetization at both temperatures. The maximum magnetic ordering temperature of ~297.7 K was found for the composition BaFe5.84Ga6.19O19 with a B-sub-lattice average ionic radius of ~7.586 Å in a field of 500 Oe. A maximum saturation magnetization of ~24.7 emu/g was found for the composition BaFe5.84Ga6.19O19 with a B-sub-lattice average ionic radius of ~7.586 Å at 50 K. A maximum hysteresis loop squareness of ~0.72 was found for the composition BaFe6.11Al1.56Cr2.17Ga2.16O19 with an average ionic radius of ~7.449 Å at 50 K. A maximum magnetic crystallographic anisotropy coefficient of ~2.09 × 105 Erg/g was found for the composition BaFe6.19Al1.25Cr1.57Ga1.74In1.26O19 with a B-sub-lattice average ionic radius of ~7.706 Å at 50 K. The frustrated magnetic state including the nano-sized clusters with an average diameter in the range of 50-200 nm was established from the results of measuring the ZFC and FC temperature magnetizations. The interpretation of the obtained experimental data is carried out taking into account the increased stability of high-entropy phases and regular changes in the intensity of the Fe3+(Al3+, Cr3+, Ga3+, In3+)-O2--Fe3+(Al3+, Cr3+, Ga3+, In3+) indirect superexchange interactions as a result of magnetic dilution of the iron sub-lattice in the magnetoplumbite structure.

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

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.

In Vivo Accelerator-Based Boron Neutron Capture Therapy for Spontaneous Tumors in Large Animals: Case Series.

(1) Background: accelerator-based neutron sources are a new frontier for BNCT but many technical issues remain. We aimed to study such issues and results in larger-animal BNCT (cats and dogs) with naturally occurring, malignant tumors in different locations as an intermediate step in translating current research into clinical practice. (2) Methods: 10 pet cats and dogs with incurable, malignant tumors that had no treatment alternatives were included in this study. A tandem accelerator with vacuum insulation was used as a neutron source. As a boron-containing agent, 10B-enriched sodium borocaptate (BSH) was used at a dose of 100 mg/kg. Animal condition as well as tumor progression/regression were monitored. (3) Results: regression of tumors in response to treatment, improvements in the overall clinical picture, and an increase in the estimated duration and quality of life were observed. Treatment-related toxicity was mild and reversible. (4) Conclusions: our study contributes to preparations for human BNCT clinical trials and suggests utility for veterinary oncology.

Aptamers for Addressed Boron Delivery in BNCT: Effect of Boron Cluster Attachment Site on Functional Activity.

Among the great variety of anti-cancer therapeutic strategies, boron neutron capture therapy (BNCT) represents a unique approach that doubles the targeting accuracy due to the precise positioning of a neutron beam and the addressed delivery of boron compounds. We have recently demonstrated the principal possibility of using a cell-specific 2'-F-RNA aptamer for the targeted delivery of boron clusters for BNCT. In the present study, we evaluated the amount of boron-loaded aptamer inside the cell via two independent methods: quantitative real-time polymerase chain reaction and inductive coupled plasma-atomic emission spectrometry. Both assays showed that the internalized boron level inside the cell exceeds 1 × 109 atoms/cell. We have synthesized closo-dodecaborate conjugates of 2'-F-RNA aptamers GL44 and Waz, with boron clusters attached either at the 3'- or at the 5'-end. The influence of cluster localization was evaluated in BNCT experiments on U-87 MG human glioblastoma cells and normal fibroblasts and subsequent analyses of cell viability via real-time cell monitoring and clonogenic assay. Both conjugates of GL44 aptamer provided a specific decrease in cell viability, while only the 3'-conjugate of the Waz aptamer showed the same effect. Thus, an individual adjustment of boron cluster localization is required for each aptamer. The efficacy of boron-loaded 2'-F-RNA conjugates was comparable to that of 10B-boronophenylalanine, so this type of boron delivery agent has good potential for BNCT due to such benefits as precise targeting, low toxicity and the possibility to use boron clusters made of natural, unenriched boron.

Structure and Raman Spectra of Exotic Carbon Microcrystals from Meteoritic Dust of Chelyabinsk Superbolide.

The Chelyabinsk superbolide, the largest in XXI century, which exploded on 15 February 2013 over snowy fields of Southern Urals was a historic event not just only because of its massive scale and explosive power. High-temperature, high-pressure conditions in the front shock wave caused intense ablation of the asteroid material and formation of huge amount of meteoritic dust dispersed in the atmosphere during the flyby. Massive snowfalls just few days before and after the event conserved precipitated meteoritic dust in thin layer of snow which was collected and studied later. The most intriguing and challenging material discovered in the dust was closed-shell 10−70 µm exotic polygonal graphitic carbon microcrystals of undisclosed nature. Using optical and electron microscopy and Raman spectroscopy the atomic structure of closed-shell microcrystals was thoroughly studied and their graphitic nature was revealed. It was found that some of the particles formed by multilayer graphitic polygonal shells have extensive hollows inside. Comparative microscopic and spectroscopic analysis of meteorite exotic carbon microcrystals with different graphite species, carbon onions, and diamond revealed two distinctively different closed-shell carbon particles. The first type of the particles can be attributed to carbon onions with characteristic graphite nanocrystalline basic structural units (BSU) of 49 nm lateral size and less and, probably, BSU heteroatomic termination necklace with oxygen content comparable to 1.1% and more. It was shown that the second type of unique graphitic carbon particles of a convex shape and perfect hexagonal symmetry with lateral dimensions of 14 µm correspond to multiply twinned closed-shell graphite microcrystals with polyhexacyclooctadecane (−C18−)n core wrapped by multiple layers of carbon honeycombs with low (<1%) content of oxygen termination necklace.

Dose-Dependent Suppression of Human Glioblastoma Xenograft Growth by Accelerator-Based Boron Neutron Capture Therapy with Simultaneous Use of Two Boron-Containing Compounds.

(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.

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

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.

The Measurement of the Neutron Yield of the 7Li(p,n)7Be Reaction in Lithium Targets.

A compact accelerator-based neutron source has been proposed and created at the Budker Institute of Nuclear Physics in Novosibirsk, Russia. An original design tandem accelerator is used to provide a proton beam. The neutron flux is generated as a result of the 7Li(p,n)7Be threshold reaction using the solid lithium target. A beam shaping assembly is applied to convert this flux into a beam of epithermal neutrons with characteristics suitable for BNCT. The BNCT technique is being tested in in vitro and in vivo studies, and dosimetry methods are being developed. Currently, the BNCT technique has entered into clinical practice in the world: after successful clinical trials, two clinics in Japan began treating patients, and four more BNCT clinics are ready to start operating. The neutron source proposed at the Budker Institute of Nuclear Physics served as a prototype for a facility created for a clinic in Xiamen (China). It is planned to equip the National Medical Research Center of Oncology (Moscow, Russia) and National Oncological Hadron Therapy Center (Pavia, Italy) with the same neutron sources. Due to the impending use of an accelerator neutron source for treating patients, the validation of the neutron yield of the 7Li(p,n)7Be reaction in lithium metal targets is required. The theoretical neutron yield has not been evaluated experimentally so far.

Tumor Cell-Specific 2'-Fluoro RNA Aptamer Conjugated with Closo-Dodecaborate as A Potential Agent for Boron Neutron Capture Therapy.

Boron neutron capture therapy (BNCT) is a binary radiotherapeutic approach to the treatment of malignant tumors, especially glioblastoma, the most frequent and incurable brain tumor. For successful BNCT, a boron-containing therapeutic agent should provide selective and effective accumulation of 10B isotope inside target cells, which are then destroyed after neutron irradiation. Nucleic acid aptamers look like very prospective candidates for carrying 10B to the tumor cells. This study represents the first example of using 2'-F-RNA aptamer GL44 specific to the human glioblastoma U-87 MG cells as a boron delivery agent for BNCT. The closo-dodecaborate residue was attached to the 5'-end of the aptamer, which was also labeled by the fluorophore at the 3'-end. The resulting bifunctional conjugate showed effective and specific internalization into U-87 MG cells and low toxicity. After incubation with the conjugate, the cells were irradiated by epithermal neutrons on the Budker Institute of Nuclear Physics neutron source. Evaluation of the cell proliferation by real-time cell monitoring and the clonogenic test revealed that boron-loaded aptamer decreased specifically the viability of U-87 MG cells to the extent comparable to that of 10B-boronophenylalanine taken as a control. Therefore, we have demonstrated a proof of principle of employing aptamers for targeted delivery of boron-10 isotope in BNCT. Considering their specificity, ease of synthesis, and large toolkit of chemical approaches for high boron-loading, aptamers provide a promising basis for engineering novel BNCT agents.

Shape anisotropic magnetic thrombolytic actuators: synthesis and systematic behavior study.

Thrombosis-related diseases are undoubtedly the deadliest disorders. During the last decades, numerous attempts were made to reduce the overall death rate and severe complications caused by treatment delays. Significant progress has been made in the development of nanostructured thrombolytics, especially magnetically controlled. The emergence of thrombolytic magnetic actuators, which can deliver tPA to the occlusion zone and perform mechanical disruption of the fibrin network under the application of a rotating magnetic field (RMF), can be considered for the next generation of thrombolytic drugs. Thus, we propose a systematic study of magnetic-field mediated mechanically-assisted thrombolysis (MFMMAT) for the first time. Four types of magnetic particles with different morphology and dimensionality were utilized to assess their impact on model clot lysis under different RMF parameters. Chain-like 1D and sea urchins-like 3D structures were found to be the most effective, increasing thrombolysis efficacy to nearly 200%. The drastic difference was also observed during the dissolution of 3 days old blood clots. Pure plasminogen activator had almost no effect on clot structure during 30 minutes of treatment while applying MFMMAT led to the significant decrease of clot area, thus uncovering the possibility of deep venous thrombosis therapy.