Toxic effect of C60 fullerene-doxorubicin complex towards tumor and normal cells in vitro

Abstract

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.

Study of biocompatibility effect of nanocarbon particles on various cell types in vitro

“…On the contrary, the studied C 60 fullerene stimulated the growth of HeLa cells (up to 10 %) at their low concentrations (6–12 µg/mL) after 3 h of incubation and the growth of human mesenchymal stem cells cells (up to 30 %) after 1 hour of incubation, Figures , . The similar effect was observed where the application of C 60 FAS induced stimulation of activity of lymphocytes was up to 15 % .…”

“…We could observe the significant decrease (up to 10%) in the number of viable HeLa cells and human mesenchymal stem cells cells compared with control (untreated cells) at the maximum concentration of C 60 fullerene 24 μg/mL after 24 h (for Hela cells) and 3 h (for human mesenchymal stem cells cells) of incubation, Figure 4A, B. Indeed, according to the data at such concentrations C 60 FAS does not manifest in vitro toxic effect on normal (thymocytes, macrophages and hepatocytes) and tumor (Erlich ascitic carcinoma and leukemia L1210) cells [9][10]26]. At the same time, C 60 FAS exhibits cytotoxic effect against Lewis lung carcinoma cells [27].…”

A nanocomplex of C60 fullerene with cisplatin: design, characterization and toxicity

“…The antitumor action of the C 60 +Dox nanocomplex was reported to be stronger than the sole action of Dox or С 60 fullerene in vivo [ 23 – 24 ]. Moreover, recently it was found that C 60 fullerene in C 60 +Dox nanocomplex prevents cyto- and genotoxic effects of Dox on lymphocytes in vitro [ 37 – 38 ]. Based on these results it was suggested that the mechanism of complexation could induce biological synergy for other drugs administered together with C 60 fullerene as well [ 19 , 23 ].…”

C60 Fullerene as Synergistic Agent in Tumor-Inhibitory Doxorubicin Treatment

“…The tumor-inhibitory activity of nanoparticles containing C 60 fullerene has been studied in models of murine hepatocarcinoma [ 12 ] and rat colorectal cancer and mammary carcinoma [ 3 , 13 , 14 ]. Finally, recent results indicate that C 60 fullerene complexation with Dox may be a key process leading to alteration of the antitumor effect of Dox in vitro [ 15 , 16 ].…”