Effect of Nano-Complexes Based on Vanadium Nanoparticles and Cholesterol on Immune System of Tumor-Bearing Animals
摘要
The interaction of the immune system cells with tumor is a delicate balance between the immune activation and immune suppression processes. There are papers demonstrating the role of vanadium compounds in the T-cell signaling regulation, which allows them to be considered as promising antitumor drugs. The purpose of research was to evaluate the effect of nanocomplexes based on GdYVO4:Eu3+ nanoparticles and cholesterol on the growth of Ehrlich ascites carcinoma and changes in immune system indices of tumor-bearing recipients. In peritoneal cavity of the Balb/c mice there were grown both native tumor cells and those pre-incubated with nanocomplexes. Healthy animals were used as controls. In the animals on the days 4, 7 and 14 after inoculation, the accumulation of the tumor cells was determined. The immune system indices were studied by assessing the number of: monocytes, M1 and M2 macrophages, T-helpers, T-suppressors, T-regulatory and natural killer cells. It was established that on day 4 the type of polarization of macrophages in peritoneal cavity was M1-like, but as the tumor grew, it turned into M2-like (days 7–14). Starting from the 7th day of the tumor development, the number of all determined subpopulations of immune competent cells gradually decreased in the lymph nodes, with the exception of the concentration of the subpopulation of T-regulatory cells, which became 1.5 times higher than in the control. Such a redistribution of immune competent cells against the background of an increased number of tumor cells in peritoneal cavity indicates the gradual development of the immune depressive state of tumor-bearing animals, that creates favorable conditions for further expansion of Ehrlich carcinoma. Cultivation of tumor cells, pre-treated with nanocomplexes, was accompanied by a decrease in both the absolute number of tumor cells and an increase in the rate of migration of monocytes to the peritoneal cavity. It is significant that such events occurred against the background of the predominant polarization of macrophages towards the pro-inflammatory M1 phenotype as well as an increase in the number of natural killer cells and a decrease in the content of T-regulatory cells in the lymph nodes. It seems that nanocomplexes are able not only to destroy, but also to change the structure of tumor cells, leading their increased immunogenicity, which was accompanied by the manifestation of prolonged life span of tumor-bearing animals.