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Information × Registration Number 0217U006894, 0115U002934 , R & D reports Title Testing of carbon-protein constructs for targeted delivery of anticancer drugs. popup.stage_title Head Sydorenko Myhail V., Registration Date 21-12-2017 Organization Department of Biotechnical Problems of Diagnostics Institute of Cryobiology and Cryomedicine of NAS of Ukraine popup.description2 Abstract. Research report: 40 pages, 9 figures, 3 tables, 31 source of the cited literature. The object of the study is a line of tumor cells of the colon carcinoma, multilayered carbon nanotubes, Doxorubicin. The aim of the work is to study the prospects of using multilayered carbon nanotubes for targeted delivery of antitumor drugs, comparison with the qualities of diamond-like and onion-like carbon. Methods of research - methods of cell culture, cyto-morphological, MTT-test, microscopy, biochemical and hematological blood tests. As a result of the third stage of the research work, a carbon compound functionalized with an antitumor drug and a fluorescent label was obtained. When studying the effect of the obtained substances on the line of tumor cells HT29, it was noted that BNToch and BHT-Dock have a moderate cytotoxic effect at concentrations of 12.5 ?g / ml. When the concentration is increased to 25-50-100 ?g / ml, the viability of tumor cells decreases dose-dependently. When the concentration of CNTs was increased to 200 ?g / ml, the viability of HT29 dropped to 39.2%. A BTN-Doc (200 ?g / ml) had even less cytotoxicity compared to BHToch, 50% with respect to control. Simultaneously, CNTs functionalized with a fluorescent label had a relatively larger cytotoxic effect on tumor cells. Thus, at a CNT-FITC concentration of 25 ?g / ml, cell survival decreased to 55%, and at 100-200 ?g / ml to 23% and 7%, respectively. On a spheroidal culture, it was demonstrated that BNTOs can stimulate BPS formation by almost 10 times. The CNT derivatives do not have such an effect on tumor cells, while BHT-DOX stimulates BPS formation 2.83 times. Co-incubating the 3D culture of tumor cells with CNT-FITC results in a decrease in the volume of BPS by 2.4-fold. In most of the experiments, BHT-Doc has no cytotoxic effect on tumor cells in both 2D and 3D cultures, which could be compared with the effects of individual Doxorubicin. But the combined use of trypsin and BHT-Doc significantly increases the cytotoxic effect of CNT and Doxorubicin in comparison with the effects of these substances separately. In the study of the effect of BHTh and BHT-Dock in vivo, the greatest effect was found on hepatic enzymes. So, ACT activity decreased more than 10 times. In this case, Doxorubicin has a similar effect. The activity of alkaline phosphatase during parenteral administration of BNToch and BHT-DOX remained almost unchanged, and when Doxorubicin was administered, it increased 1.6-fold. In addition to BNTokh, Doxorubicin and BHT-Doc slightly reduced the level of albumin and total protein in the blood of experimental animals. In hematological studies, signs of hematologic toxicity of BNToch and BHT-Dock were detected: anemia (decrease in the number of erythrocytes, hemoglobin, hematocrit), thrombocytopenia (decrease in the number of platelets), neutropenia (decrease in the number of granulocytes). In addition, the same orientation of changes in almost all hematological parameters in groups of animals receiving BHTh and BHT-Dock was found. However, the severity of changes in the groups of animals treated with BHT-Doc is statistically significantly higher. Thus, based on the results obtained, we assume that the resulting compound (BHT-Doc) is capable of carrying the drug into the cellular microenvironment without causing a significant cytotoxic effect. In the presence of peptidase (trypsin), Doxorubicin is released and its cytotoxic effect is increased. This effect was observed in experiments both in vitro and in vivo. Key words: Tumor cells of colon carcinoma, carbon nanotubes, doxorubicin, adhesion, proliferation. Product Description popup.authors Гергелюк Тетяна Сергіївна Нестеренко Олена Михайлівна Перепелиціна Олена Михайлівна Сидоренко Михайло Васильвич Ястребова Олена Вікторівна popup.nrat_date 2020-04-02 Close