A.E. Lugovtsov, M.V. Lomonosov Moscow State University, Moscow, Russia
G. Barshtein, The Hebrew University of Jerusalem, Jerusalem, Israel
V.I. Kochubey, Saratov State University, Saratov, Russia
E.A Shirshin, M.V. Lomonosov Moscow State University, Moscow, Russia
V.V. Tuchin, Saratov State University, Saratov, Russia
C.L. Cheng, National Dong Hwa University, Hualien, Taiwan
A.V. Priezzhev, M.V. Lomonosov Moscow State University, Moscow, Russia
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), which is perspective for medical applications (fullerenes, nanodiamonds (ND), iron oxide Fe2O3, TiO2, Si nanoparticles and others), with rat and human red blood cells (RBC). Particular attention was paid to the effect of NP on the mechanical and microrheological properties of RBC. It is expected that the results of the study of the interaction of these and other 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 on EDTA stabilized 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 is dependent on the particle concentration, size, and surface functionalization. The alterations in RBC ability to deform (microrheological properties) are more significant for higher NP concentrations and more pronounced for non-functionalized particles, for example for Fe2O3-NP functionalized with porphyrin and carboxylated ND.
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 the 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. Basing on the results one can conclude that the NP can be administered into the blood in ambient conditions at low concentrations (33 μg/ml), without the significant complication of the blood rheological conditions.
This work was supported by Russian Foundation of Basic Research grant (№ 17-02-01200).
Dr. Andrei Egorovich Lugovtsov
International Laser Center of M.V. Lomonosov Moscow State University, Ph.D., reseacher
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