Boron carbide is one of the hardest materials in the world which can be synthesized by various methods. The most common one is a carbothermic or magnesiothermic reduction of B₂O₃ performed at high temperatures, where the obtained powder still requires grinding and purification. The goal of this research is to present the possibility of synthesizing B₄C nanoparticles from elements via vapor deposition and modifying the morphology of the obtained powders, particularly those synthesized at high temperatures. B₄C nanoparticles were synthesized in the process of direct synthesis from boron and carbon powders heated at the temperature of 1650 °C for 2 h under argon and characterized by using scanning electron microscopy, transmission electron microscopy, atomic force microscopy, X-ray diffraction analysis, and dynamic light scattering measurements. The physicochemical characteristics of B₄C nanoparticles were determined, including the diffusion coefficients, hydrodynamic diameter, electrophoretic mobilities, and zeta potentials. An evaluation of the obtained B₄C nanoparticles was performed on several human and mouse cell lines, showing the relation between the cytotoxicity effect and the size of the synthesized nanoparticles. Assessing the suitability of the synthesized B₄C for further modifications in terms of its applicability in boron neutron capture therapy was the overarching goal of this research.

The main purpose of our study was to determine the effect of dendritic cell (DC) transduction with lentiviral vectors carrying sequences of il18 and/or il12 genes on the level of antitumor activity in vitro and in vivo. We examined the ability of DCs to migrate to the tumor-draining lymph nodes and infiltrate tumor tissue and to activate the local and systemic antitumor response. On the 15th day, DCs genetically modified for production of IL-12 and/or IL-18 were administered peritumorally to C57BL/6 female mice with established MC38 tumors. Lymphoid organs and tumor tissue were collected from mice on the 3rd, 5th, and 7th days after a single administration of DCs for further analysis. Administration of DCs transduced for production of IL-12 alone and in combination with IL-18 increased the inflow and activity of CD4⁺ and CD8⁺ T lymphocytes in the tumor microenvironment and tumor-draining lymph nodes. We also found that even a single administration of such modified DCs could trigger a systemic antitumor response as well as inhibit tumor growth. Application of the developed DC-based vaccines may exert a favorable impact on stimulation of an antitumor immune response, especially if these DC vaccines are administered repeatedly.

In this research, we developed boron-rich nanoparticles that can be used for boron neutron capture therapy as potential carriers for boron delivery to cancerous tissues. Functionalized carbonated boron nitride nanostructures (CBNs) were successfully synthesized in self-propagating combustion waves in mixtures of high-nitrogen explosives and boron compounds. The products’ composition, morphology, and structural features were investigated using Fourier transform infrared spectroscopy, powder X-ray diffraction, low-temperature nitrogen sorption analysis, thermogravimetric analysis, high-resolution scanning electron microscopy, and high-resolution transmission electron microscopy. The extreme conditions prevailing in combustion waves favor the formation of nanosized CBN hollow grains with highly disordered structures that are properly functionalized on the surface and inside the particles. Therefore, they are characterized by high porosity and good dispersibility in water, which are necessary for medical applications. During biological tests, a concentration-dependent effect of the obtained boron nitride preparations on the viability of normal and neoplastic cells was demonstrated. Moreover, the assessment of the degree of binding of fluorescently labeled nanoparticles to selected cells confirmed the relationships between the cell types and the concentration of the preparation at different incubation time points.

Lipopolysaccharides are the main surface antigens and virulence factors of gram-negative bacteria. Removal of four ester-bound fatty acid residues from hexaacyl lipid A of Escherichia coli lipooligosaccharide (LOS) resulted in the de-O-acylated derivative E. coli LOS-OH (LOS-OH). This procedure caused a significant reduction in the toxicity of this compound compared to the native molecule. We investigated the effect of such a structural LOS modification on its biological activity using in vitro assays with monocytic cells of the RAW264.7 line, dendritic cells of the JAWS II line, bone marrow-derived dendritic cells (BM-DCs), and spleen cells. Furthermore, in in vivo experiments with a melanoma B16 metastasis model, the anti-metastatic activity of the compounds and spleen cell reactivity mediated by them representing a systemic response were analyzed. The results revealed that LOS-OH demonstrated weaker ability than LOS to stimulate and polarize an immune response both in vitro and in vivo. It induced lower cytokine production by cells of myeloid lines. Multiple applications of LOS-OH into mice injected intravenously with B16 cells significantly (P<0.05; P<0.01) reduced the number of metastatic foci in the lungs, presumably via silencing of myeloid cell reactivity as well as the inability to stimulate lymphoid cells both directly and indirectly. These findings suggest that LOS-OH maintained in the body of metastasis-bearing mice appears to modulate or downregulate the innate response, leading to the inability of blood myeloid cells to support the migration of melanoma cells to lung tissue.

Background: Boron neutron capture therapy (BNCT) is a type of targeted radiotherapy that destroys boron-containing cancer cells using a neutron beam. It is intended for the treatment of patients with tumors that are resistant to conventional treatment, inoperable and recurrent. Therefore, it represents a promising therapy for the treatment of glioblastoma multiforme, the most aggressive stage IV cancer. To ensure high efficacy of BNCT, it is necessary to use selective boron carriers that deliver therapeutic doses of the boron-10 isotope to the tumor site, demonstrate a lack of systemic toxicity, and, most importantly, cross the blood-brain barrier. In our studies, we propose using bone marrow-derived macrophages as cellular carriers of boron carbide nanoparticles to selectively deliver boron-10 to the tumor microenvironment. Macrophages can efficiently engulf foreign particles, migrate and accumulate at the tumor site, as well as cross the blood-brain barrier, making them extremely promising boron carriers for BNCT. Results: Bone marrow-derived macrophages in three polarization states (M0, M1, and M2) demonstrated a high uptake ability of boron carbide nanoparticles at a concentration of 100 µg/ml during 24-hour incubation. The highest boron concentration was detected in M1 macrophages, resulting in the greatest inhibition of viability and slower spontaneous migration of this population compared to other types of macrophages. Nevertheless, all macrophage populations (M0, M1, and M2) loaded with boron carbide nanoparticles migrated comparably through the brain endothelial cell layer, mimicking the blood-brain barrier, toward the CCL2-rich supernatant of GL-261 glioma cells. Furthermore, macrophages with nanoparticles did not affect the viability of glioma spheroids after 6 days of co-culture, in contrast to macrophages without nanoparticles, which increased the survival of tumor cells. Importantly, M1 macrophages did not repolarize toward the M2 phenotype during co-culture, as evidenced by the stable expression of CD206 in these cells. In addition, M2 macrophages loaded with B ₄ C nanoparticles showed lower CD206 expression after contact with spheroids compared to this macrophage population without nanoparticles. Conclusions: Bone marrow-derived macrophages loaded with boron carbide nanoparticles showed great potential for use in BNCT as boron carriers crossing the blood-brain barrier toward the glioma microenvironment.