The main aim of this work was to evaluate the effect of doxorubicin in complex with C60 fullerene (C60 + Dox) on the growth and metastasis of Lewis lung carcinoma in mice and to perform a primary screening of the potential mechanisms of C60 + Dox complex action. We found that volume of tumor from mice treated with the C60 + Dox complex was 1.4 times less than that in control untreated animals. The number of metastatic foci in lungs of animals treated with C60 + Dox complex was two times less than that in control untreated animals. Western blot analysis of tumor lysates revealed a significant decrease in the level of heat-shock protein 70 in animals treated with C60 + Dox complex. Moreover, the treatment of tumor-bearing mice was accompanied by the increase of cytotoxic activity of immune cells. Thus, the potential mechanisms of antitumor effect of C60 + Dox complex include both its direct action on tumor cells by inducing cell death and increasing of stress sensitivity and an immunomodulating effect. The obtained results provide a scientific basis for further application of C60 + Dox nanocomplexes as treatment agents in cancer chemotherapy.

In vitro experiments have shown that C60 fullerenes exhibit cytotoxic effects against tumor cells and modulate the cytotoxic activity of immune cells. In vivo therapeutic experiments on the model of Lewis lung carcinoma showed that C60 fullerenes exhibit an antimetastatic effect (reduction of metastases by 27%), which is realized by activating macrophages and stimulating the synthesis of humoral factors, which significantly increase the cytotoxicity of treated animals serum.

Creation of new nanostructures possessing high antitumor activity is an important problem of modern biotechnology. Aim. To evaluate cytotoxicity of created complex of pristine C 60 fullerene with the anthracycline antibiotic doxorubicin (Dox), as well as of free C 60 fullerene and Dox, towards different cell types-tumor, normal immunocompetent and hepatocytes. Methods. Measurement of size distribution for particles in C 60 + Dox mixture was performed by a dynamic light scattering (DLS) technique. Toxic effect of C 60 + Dox complex in vitro towards tumor and normal cells was studied using the MTT assay. Results. DLS experiment demonstrated that the main fraction of the particles in C 60 + Dox mixture had a diameter in the range of about 132 nm. The toxic effect of C 60 + Dox complex towards normal (lymphocytes, macrophages, hepatocytes) and tumor (Ehrlich ascites carcinoma, leukemia L1210, Lewis lung carcinoma) cells was decreased by~10-16 % and~7-9 %, accordingly, compared with the same effect of free Dox. Conclusions. The created C 60 + Dox composite may be considered as a new pharmacological agent that kills effectively tumor cells in vitro and simultaneously prevents a toxic effect of the free form of Dox on normal cells.

Aim. To study the chemical composition, sugar specificity and physicochemical properties of the extracellular lectin isolated from Bacillus subtilis ІМV В-7724. Methods. Biochemical, spectrophotometric, immunological and cultural methods were used to assess the physicochemical and a number of biological properties of lectin isolated from the culture fluid of bacteria B. subtilis ІМV В-7724. Molecular weight of the lectin was estimated in polyacrylamide gel electrophoresis. Analysis of the elemental composition was done using Perkin-Elmer 2400 CHNS analyzer. Temperature and pH stability of lectin were examined based on residual hemagglutination activity of the lectin. Cytotoxic activity was determined by the MTT-assay. The statistical analysis was made using Student’s t-test. Results. B. subtilis IMV B-7724 lectin is a glycoprotein (protein – 86.0%, carbohydrates – 7.0%) with molecular weight of 18–20 kDa (major). Analysis of the elemental composition revealed that it contains 34.00% of carbon, 7.04% of hydrogen, 16.61% of nitrogen, 42.35% of oxygen. Amino acid composition analysis determined that it is rich in leucine, tyrosine and phenylalanine. The lectin exhibited high sugar-binding specificity toward N-acetylneuraminic and N-glycolylneuraminic acids (minimal inhibitory concentration – 0.3 mM for both sugars). The lectin is heat and acid stable, has long shelf life. Conclusions. These results provide the rationale to pursue further investigation for possible ways and modes of B. subtilis IMB B-7724 lectin application in clinical settings.

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