Nanotechniques Inactivate Cancer Stem Cells

Abstract

One of the tasks of current oncology is identification of cancer stem cells and search of therapeutic means capable of their specific inhibition. The paper presents the data on phenotype characteristics of Ehrlich carcinoma cells as convenient and easy-to-follow model of tumor growth. The evidence of cancer stem cells as a part of Ehrlich carcinoma and significance of CD44+ and CD44– subpopulations in maintaining the growth of this type of tumor were demonstrated. A high (tenfold) tumorigenic activity of the Ehrlich carcinoma CD44+ cells if compared to CD44– cells was proven. In this pair of comparison, the CD44+ cells had a higher potential of generating in peritoneal cavity of CD44high, CD44+CD24–, CD44+CD24+ cell subpopulations, highlighting the presence of cancer stem cells in a pool of CD44+ cells.In this study, the ability of synthesized hybrid nanocomplexes, comprising the nanoparticles of rare earth orthovanadates GdYVO4:Eu3+ and cholesterol to inhibit the tumor growth and to increase the survival of the animals with tumors was established. A special contribution into tumor-inhibiting effect is made by each of its components. Treatment of Ehrlich carcinoma cells with two-component hybrid complex resulted in maximum reduction in the concentration of the most tumorigenic CD44high cells with simultaneous rise in the number of CD117+ cells that decreased an intensity of tumor growth by 74.70 ± 4.38% if compared with the control.

Nanocomposites specifically penetrate and inhibit tumor cells

“…Malignant neoplasms were proven to be resulted from the formation and expansion of small population of cancer stem cells able of unlimited self‐renewal . It is proven that in the Ehrlich carcinoma development in a simulated breast cancer, the fraction of CD44 + ‐cells, isolated by immunomagnetic sorting had an increased tumorigenic potential . The separation purity of CD44 + ‐fraction made not less than 90 %.…”

“…The Ehrlich carcinoma cells cryopreserved in ascetic fluid were used as the primary culture . After thawing, they were transplanted in vivo three times in order to mitigate the freeze‐thawing influence and gaining by them of morphological and functional characteristics of native cells . The “stabilized” Ehrlich carcinoma cells were intraperitoneally injected into mice in 0.03 × 10 8 cells dose in 0.3 ml physiological solution and incubated for 7 days in peritoneal cavities.…”

“…The “stabilized” Ehrlich carcinoma cells were intraperitoneally injected into mice in 0.03 × 10 8 cells dose in 0.3 ml physiological solution and incubated for 7 days in peritoneal cavities. The development of Ehrlich carcinoma was considered to be sufficient if at day 7 the total number of cells in mice peritoneal cavities was at least 3.5 × 10 8 . Later, these cells were the object of study.…”

“…Total suspension of Ehrlich carcinoma cells and CD44 + fraction with hybrid nanocomplexes or nanoparticles was incubated in 5 % glucose solution (Infusion JSC, Ukraine) at room temperature for 3 h. Such an incubation time was previously determined to be optimal for binding nanocomplexes to cell membranes .…”

“…This is facilitated by the presence of a large amount of scavenger receptor class B type I and caveolin‐1 receptors capable of binding with free cholesterol from the bloodstream on the tumor cell surface . It has been shown that the addition of the dye DiI to hybrid nanocomplexes allows the visualization of almost all cells with a CD44 + phenotype in Ehrlich carcinoma cells . This model pathology is a convenient object for experimental studies of the influence of various factors and therapeutic agents directly on cancer cells, as these are undifferentiated cells of in vivo transplanted mice breast cancer .…”