The development of new methods increasing the biological effectiveness of proton therapy (PT) is of high interest in radiation oncology. The use of binary technologies, in which the damaging effect of proton radiation is further enhanced by the selective accumulation of the radiosensitizer in the target tissue, can significantly increase the effectiveness of radiation therapy. To increase the absorbed dose in a tumor target, proton boron capture therapy (PBCT) was proposed based on the reaction of proton capture on the ¹¹B isotope with the formation of three α-particles. This review summarizes data on theoretical and experimental studies on the effectiveness and prospects of proton boron capture therapy.

The potential of standard methods of radiation therapy is limited by the dose that can be safely delivered to the tumor, which could be too low for radical treatment. The dose efficiency can be increased by using radiosensitizers. In this study, we evaluated the sensitizing potential of biocompatible iron oxide nanoparticles coated with a dextran shell in A172 and Gl-Tr glioblastoma cells in vitro. The cells preincubated with nanoparticles for 24 h were exposed to ionizing radiation (X-ray, gamma, or proton) at doses of 0.5–6 Gy, and their viability was assessed by the Resazurin assay and by staining of the surviving cells with crystal violet. A statistically significant effect of radiosensitization by nanoparticles was observed in both cell lines when cells were exposed to 35 keV X-rays. A weak radiosensitizing effect was found only in the Gl-Tr line for the 1.2 MeV gamma irradiation and there was no radiosensitizing effect in both lines for the 200 MeV proton irradiation at the Bragg peak. A slight (ca. 10%) increase in the formation of additional reactive oxygen species after X-ray irradiation was found when nanoparticles were present. These results suggest that the nanoparticles absorbed by glioma cells can produce a significant radiosensitizing effect, probably due to the action of secondary electrons generated by the magnetite core, whereas the dextran shell of the nanoparticles used in these experiments appears to be rather stable under radiation exposure.

Type I interferons, particularly IFNα-2b, play essential roles in eliciting adaptive and innate immune responses, being implicated in the pathogenesis of various diseases, including cancer, and autoimmune and infectious diseases. Therefore, the development of a highly sensitive platform for analysis of either IFNα-2b or anti-IFNα-2b antibodies is of high importance to improve the diagnosis of various pathologies associated with the IFNα-2b disbalance. For evaluation of the anti-IFNα-2b antibody level, we have synthesized superparamagnetic iron oxide nanoparticles (SPIONs) coupled with the recombinant human IFNα-2b protein (SPIONs@IFNα-2b). Employing a magnetic relaxation switching assay (MRSw)-based nanosensor, we detected picomolar concentrations (0.36 pg/mL) of anti-INFα-2b antibodies. The high sensitivity of the real-time antibodies’ detection was ensured by the specificity of immune responses and the maintenance of resonance conditions for water spins by choosing a high-frequency filling of short radio-frequency pulses of the generator. The formation of a complex of the SPIONs@IFNα-2b nanoparticles with the anti-INFα-2b antibodies led to a cascade process of the formation of nanoparticle clusters, which was further enhanced by exposure to a strong (7.1 T) homogenous magnetic field. Obtained magnetic conjugates exhibited high negative MR contrast-enhancing properties (as shown by NMR studies) that were also preserved when particles were administered in vivo. Thus, we observed a 1.2-fold decrease of the T2 relaxation time in the liver following administration of magnetic conjugates as compared to the control. In conclusion, the developed MRSw assay based on SPIONs@IFNα-2b nanoparticles represents an alternative immunological probe for the estimation of anti-IFNα-2b antibodies that could be further employed in clinical studies.

Magnetic parameters of magnetosomes inside the bacteria of MSR-1, LBB-42, AMB-1, SP-1, BB-1, and SO-1 strains of the genus Magnetospirillum fixed by 5% formalin in the nutrient medium were estimated by measurements of the nonlinear longitudinal response to a weak ac magnetic field (NLR-M2) at room temperature. For the BB-1, MSR-1, and AMB-1 strains, the measurements of the electron magnetic resonance (EMR) spectra with the special X-band spectrometer for wide-line registration were also carried out. To trace the evolution of the magnetic state of the magnetosomes during the long-term storage, freshly prepared samples (“new”) and samples after a year of storage at 4 °C (“old”) were studied. The assessment of the state of the bacteria ensemble in the medium after the long-term storage was carried out for one typical strain (BB-1) using atomic force microscopy. The stable single-domain state of magnetic centers in the magnetosomes indicating their proximity to a superparamagnetic (SPM) regime was found at the scan frequency 0.02 Hz of the steady magnetic field. This allowed a semi-quantitative analysis of M2 data to be carried out with the formalism based on the numerical solution of the kinetic Fokker–Planck equation for SPM particles. Processing the NLR-M2 data demonstrated the presence of two kinds of magnetosomes in both the “new” and “old” samples: (i) those with the large magnetic moment (the “heavy”, monodisperse mode) and (ii) those with the comparatively small magnetic moment (the “light”, highly dispersed mode). The EMR spectra were formed mostly by the “heavy” fraction for both samples. The presence of two peaks in the spectra evidenced the presence of conventional uniaxial magnetic anisotropy in the magnetosomes. The appearance of one or two additional peaks in the spectra in the “old” fraction of some strains implied their instability at the long-term storage, even when fixed by formalin and sealed in the nitrogen atmosphere.

For therapeutic applications it is important to know quantitative uptake of nanoparticles by the cells. In this work incorporation of superparamagnetic iron oxide nanoparticles (SPIONs) coated by the dextran shell into malignant glioma cells, as well as into human fibroblast cells in vitro was studied. Nanoparticles were synthesized by co-precipitation and the presence of chemical impurities in them was assessed by X-ray fluorescence measurements. Geometrical parameters of nanoparticles were characterized by X-ray diffraction and dynamic light scattering. Magnetic and dynamic parameters of SPIONs in the medium before co-incubation with cells as well as in cells after incubation were found using highly sensitive method of nonlinear response to a weak ac magnetic field parallel to the steady field with registration of the second harmonic of magnetization M₂ followed by processing the obtained data with the formalism based on the Gilbert-Landau-Lifshitz equation for stochastic dynamics of superparamagnetic particles. The formation of SPION aggregates in the incubation medium was established, accompanied by a decrease in magnetostatic and, accordingly, free energy of the SPIONs system. The uptake of SPIONs by the cells at co-incubation was studied depending on the concentration of nanoparticles, duration of the co-incubation and the seeding density. The data obtained indicate: (i) close values of the magnetic and dynamic parameters of nanoparticle aggregates absorbed by the cells and in the medium before incubation; (ii) the decrease in the amount of SPIONs absorbed by cells at a higher seeding density; (iii) dependence of the SPIONs uptake on their concentration (characterized by the iron content) in the medium and on the time of co-incubation as well as on the cell type, with minimal uptake by cells of normal morphology.