Investigation of effect of EMAP II cytokine nanocomposite complex with dextran 70 on the BALB/C mice lines

Abstract

The cytokine ЕМАР ІІ is endothelial and monocytic-activating polypeptide II, the precursor of which is the component of the high-molecular complex aminoacyl-tRNA synthetase of the higher eukaryotes of the protein p43, is capable of modulating the properties of endothelial cells, monocytes and leukocytes. In low concentrations the cytokine stimulates and in high concentrations it suppresses the migration of endothelial cells, stimulates their apoptosis, affects the activity of monocytes, neutrophils, macrophages, thus contributing to inflammatory and necrotic processes in malignant tumors. One of the promising directions of targeted therapy of oncological diseases is the use of antiangiogenic, prokoagulative and proapoptic drugs, which became the basis for the selection of an antitumor cytokine ЕМАР ІІ as an object of research. In the Institute of Molecular Biology and Genetics of the National Academy of Sciences of Ukraine, the biotechnology of bacterial expression of recombinant ЕМАР ІІ in E.coli BL21 (DE3) cells and isolation of highly purified cytokine preparations in preparative amounts have been developed. In order to increase the stability and reduce the aggregation of recombinant ЕМАР ІІ, scientific and methodological foundations were created and nanocomposite complexes of the cytokine EMAR II with biocompatible polymers with cyclodextrin and dextran 70 were obtained. In this experimental work, the effects of the nanocomposite complex EMAR II and dextran-70 on the animal organism were investigated for the purpose of establishing safety of its use. BALB / C mice were used as an object of research. Experimental studies have shown that acute and chronic administration of the drug to animals at doses of 300 – 10 000 μg / kg does not show the general toxic effects of the nanocomposite complex on the organism of mice. The obtained data open the prospect of further investigation of antitumor properties of the nanocomposite complex EMAR II with dextran-70 with the aim of possible further introduction into pharmacological practice.