Issues

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2020

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vol. 18 /

Issue 3

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А. М. Goltsev, Yu. V. Malyukin, N. M. Babenko, Yu. O. Gaevska, M. O. Bondarovich, M. V. Оstankov, I. F. Kovalenko, V. K. Klochkov
«Antitumor Efficiency of Hybrid Nanocomplexes Depends on the Time of Their Interaction with Ehrlich Carcinoma Cells»
487–503 (2020)

PACS numbers: 81.16.Fg, 87.15.hg, 87.15.K-, 87.19.xj, 87.64.kv, 87.64.mk, 87.85.Rs

The significance of an incubation time of tumour cells with hybrid nanocomplexes (NCs) based on nanoparticles of orthovanadates of the rare-earth elements GdYVO\(_4\): Eu\(^{3+}\) and cholesterol in inhibiting the growth of Ehrlich’s adenocarcinoma (EAC) is shown. The EAC cells were incubated with NCs for 1, 2, 3, and 4 hours, afterwards, their accumulation in cells was evaluated using a LSM 510 META confocal laser microscope, and there were assessed mitochondrial respiration (MTT test) as well as number of apoptotic/necrotic cells. Using confocal microscopy, it is possible to determine the dynamics and degree of accumulation of NCs in different subpopulations of EAC cells. It is established that NCs are able to contact only individual EAC subpopulations. The fluorescence intensity of NCs in EAC cells approaches the maximum at 3 hours of incubation, which is accompanied by a significant decrease in cell mitochondrial respiration and a statistically significant increase in late apoptosis (An\(^{+}\)/PI\(^{+}\)) and necrosis (An\(^{-}\)/P\(^{+}\)) cells compared with the control. Such changes in EAC cells in vitro contributed to the maximum implementation of the NCs antitumour effect in vivo, judging by the inhibition of tumour growth, were maximal after about three hours of incubation and were about 70%. The predominant accumulation of NCs in the CD44\(^{+}\) subpopulation of EAC with ultrahigh expression intensity of this marker (CD44\(^{high}\)-cells) is established. This confirms that the implementation of the antiproliferative properties of hybrid NCs can be accomplished by inhibiting the function of tumour cells with stem potential. The ability of NCs to simultaneously visualize tumour cells and inhibit its growth makes it possible to consider this type of nanomaterials as promising theranostic agents.

Keywords: Ehrlich’s adenocarcinoma cells, nanocomplexes, confocal microscopy

https://doi.org/10.15407/nnn.18.03.487

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