Alexander V. Priezzhev and Andrei E. Lugovtsov (Moscow State University, Russia), Victoria G. Ionova, (Institute of Neurology of RAMN, Russia), Chia-Liang Cheng and Elena Perevedentseva (National Dong Hwa University, Taiwan)
Nanodiamond particles (NDs) are perspective fluorescent markers that can potentially be used for biomedical diagnostics. Although they seem to be not toxic and not to destroy vitally important organs, tissues and cells as was shown in a number of biological experiments both in vitro and in vivo, their implementation into clinical experiments is highly debated nowadays.
The aim of our work was to study the effect of NDs on blood microrheology, in particular, on the ability of red blood cells (RBCs) to deform in shear flow and to spontaneously aggregate. This was motivated by the fact that the administration of NDs and other nanoparticles into a live organism is usually performed intravenously, i.e. via blood vessels. However the effect of nanoparticles on blood and on its ability to normally flow though the vessels of different radii is usually not accounted for. In particular, administration of nanoparticles into blood can potentially lead to the reduction of RBC deformability which may further lead to the impairments of the blood flow through smaller vessels.
In order to study the effect of NDs on RBCs we have conducted a series of in vitro measurements of the deformability index and several parameters of aggregation kinetics using the optical measurement techniques based on the detection of diffraction patterns from dilute suspensions of RBCs and diffuse reflection from a layer of whole blood. In our experiments, we used suspensions of NDs with sizes from 5 to 500 m in bidistilled water of different concentrations, added to samples of freshly drawn human blood. The ND particles were either bare or corboxilated (cND) to improve their biocompatibility.
We have shown the there is a remarkable negative effect of NDs and cNDs on both deformability and aggregation kinetics of RBCs in the in vitro experiments. The effect is concentration dependent. In particular, smaller NDs and cNDs (around 5 m characteristic size) in smaller concentrations (around 33 mg/ml) seem to decrease the time of formation of both linear and 3D RBC aggregates and enhance the amplitude of spontaneous RBC aggregation in whole blood, which are overall negative physiologic effects. Larger NDs and cNDs (around 500 m characteristic size) as well as smaller ones in higher concentrations (around 330 mg/ml) lead to smaller negative effects which can be speculated as a result of small particles aggregation in concentrated suspensions and nonpenetration of relatively large ND particles and their aggregates into the RBCs through their membranes. Carboxilation of ND particle surface makes the negative effect of small cNDs less pronounced but does not totally abolish it.
The effect of ND particles on shear deformability of RBCs is negative as well: the RBC deformability index is reduced all through the range of shear stresses (from 3 to 60 Pa). However the reduction of the defomability index becomes evident at higher concentrations (around 100 mg/ml).
These initial results are indicative of the importance of thorough studies of the effect of nanoparticles on blood rheologic properties, given the particles are to be delivered to the targets via the blood flow. The effect of nanoparticles on the macromolecules constituting the blood plasma is still an open issue, which should be studied as well, because blood proteins also play a significant role in RBC microrheologic properties.
Alexander V. Priezzhev, Moscow State University, prof. (, Russia)
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