Nanobiotechnology for health-care

Nanocomplexes based on rare-earth metal orthovanadates are able to change activity of self-maintenance genes in Ehrlich carcinoma cells
Goltsev A.M.1, Malyukin Yu.V.2, Babenko N.M.1, Gaevska Yu.O.1, Bondarovych M.O.1, Dubrava T.G.1, Ostankov M.V.1, Klochkov V.K.2
1  Institute for Problems of Cryobiology & Cryomedicine of the National Academy of Sciences of Ukraine, Pereyaslavska Str. 23, 61016 Kharkiv, Ukraine
E-mail:  cryo@online.kharkov.ua
2 Institute for Scintillation Materials of the National Academy of Sciences of Ukraine, 60 Nauki ave., 61001 Kharkiv, Ukraine

The search for methods to selectively recognize and inactivate the cancer stem cells with the CD44+ phenotype having tumorigenic activity is an urgent task. It was shown that hybrid nanocomplexes (NC) containing nanoparticles of the rare-earth metal orthovanadates GdYVO4:Eu3+ and cholesterol are able to inhibit the functional activity of Ehrlich carcinoma cells (EC). The implementation mechanism of this effect may be related to the modulation of the expression of self-maintaining genes in tumor cells, which was the aim of study.
The experiments were performed in cells of total population of EC, CD44+ and CD44- fractions isolated by magnetic separation (BD IMagnet, USA). The cells of each group were incubated in vitro with NC for 3 hours, and then were intraperitoneally injected to BALB / c mice (5x106 cells / mouse). On day 7, the tumor growth rate and the expression rate of nanog, oct-4, sox-2 genes were evaluated by real-time PCR. Similar groups without NC treatment were a control.
It was shown that in the control groups the CD44+ cells had the highest tumorigenic activity compared to total population and the CD44- fraction of EC, which was accompanied by an increased expression rate of all the genes studied. After pretreatment of EC cells with hybrid NC, the tumors were formed in all groups, in the cells of which the expression of the studied genes was significantly reduced compared to the control. At the same time, a strong decrease in the tumorigenic activity of the CD44+ fraction was noted, which might be associated with maximum inhibition of the key nanog gene, determining their self-maintenance. Thus, the findings may indicate the implementation of antitumor effect of orthotovanadates at the genome level.