ИСТИНА

Laser diffractometry, diffuse light scattering aggregometry, and fluorescence microscopy, as well as optical trapping were used to study various aspects of the interaction of nanoparticles (NP) perspective for medical applications, with rat and human red blood cells (RBC). In particular, we studied fullerenes, magnetic and non-magnetic nanodiamonds (ND), iron oxide Fe2O3, TiO2, Si nanoparticles and others. Special attention was paid to the effect of NP on the mechanical and microrheological properties of RBC and on their safety for biomedical applications [1, 2]. It is expected that the results of the study of the interaction of the NP with RBC and other blood cells in vitro can provide a basis for determining their cytotoxicity without conducting experiments with animals in vivo. This test will significantly reduce the need for experiments with animals when studying the effect of NPs on the human organism. All experimental results were obtained by laser based techniques [3] on human and rat blood samples incubated with NP of different sizes and surface functionalization in different concentrations for in vitro and in vivo conditions. It was shown that incubation of RBCs with NP at high concentrations of the latter does provoke decreasing of deformability of the cells, the effect being dependent on the particles concentration, size, and surface functionalization. The alterations in RBC ability to deform are more significant for higher NP concentrations and more pronounced for non-functionalized particles. The effect of nanomaterials on RBCs aggregation is ambiguous. Experiments conducted in vitro allow us to conclude that the iron oxide nanoparticles and fullerenes reduce the RBC aggregation, while the addition of ND enhance the aggregation of cells. These effects strongly depend on the concentration and slightly depend on surface functionalization with porphyrin and carboxylate groups of iron oxide NP and ND accordingly. To further investigate the interaction between the NPs and RBCs, namely, to study sorption onto the membrane and cellular penetration, we performed experiments using the fluorescence laser confocal microscopy. Basing on our experimental results we can conclude that it is not possible to make a general conclusion about the effect of the nanoparticles on the rheological properties of RBC. However, under certain conditions, this effect can be very significant and it is necessary to check the hemocompatibility of each sample of nanoparticles in vitro. Also, we can conclude that the NP can be administered into the blood in ambient conditions at low concentrations (not higher than 30 μg/ml), without significant complications of the blood rheological properties. The work was financially supported by the Russian Science Foundation grant No. 20-45-08004. [1] Lin Y.C. et al., The influence of nanodiamond on the oxygenation states and micro rheological properties of human red blood cells in vitro, Journal of Biomedical Optics, 17(10), pp. 101512, (2012). [2] Tsai L.-W. et al., Nanodiamonds for medical applications: Interaction with blood in vitro and in vivo, International Journal of Molecular Sciences, 17(7), pp. 111, (2016 ). [3] Lugovtsov A. E. et al., Optical assessment of alterations of microrheologic and microcirculation parameters in cardiovascular diseases, Biomedical Optics Express, 10(8), pp. 3974–3986, (2019).