Influence of Carbon Nanotubes and Its Derivatives on Tumor Cells In Vitro and Biochemical Parameters, Cellular Blood Composition In Vivo

Abstract

The aim of the proposed work was to analyze the toxicity of oxidized carbon nanotubes (CNTox), functionalized by doxorubicin (CNT-Dox) and fluorescein (CNT-FITC) on cell and organism level. The cytotoxic effect of CNTox, CNT-Dox, and CNT-FITC was analyzed on tumor cells in vitro (2-D, 3-D cultures) and on Balb2/c mice model in vivo. As a result, it was demonstrated the possibility of doxorubicin immobilization on the surface of CNT and controlled release of doxorubicin (Dox) from the surface of CNT. Dox immobilization coincident with decreasing cytotoxic effect CNT-Dox compared with free Dox. Breakdown of peptide bonds with CNT surface led to the release of doxorubicin and dose-dependent enhancement of the cytotoxic effect of CNTs and Dox. The combined cytotoxic effect from CNTs, Dox, and trypsin on the survival of tumor cells was shown. At the organism level, it was investigated the effect of the obtained nanostructures on the state of hepatic enzymatic system, the protein metabolism, and cell blood composition of the experimental animals. CNTox influence in vivo model was statistically the same as control. CNT-Dox demonstrated lower total organism toxic effect compared to the pure doxorubicin. Deviations in the cell blood composition indicated a general toxic effect of CNT-Dox, but it was more moderate compared with of pure doxorubicin. From the data obtained, we concluded that binding CNTs with doxorubicin allows reducing toxicity of the doxorubicin on the general biochemical indicators of blood and violations in the blood cells composition in vivo. At the same time, the combined effect of CNTs and doxorubicin after drug release allowed us to achieve greater efficacy in suppressing tumor growth in vitro.