Abstract
Cisplatin (Cis-Pt) is the cytotoxic agent widely used against tumors of various origin, but its therapeutic efficiency is substantially limited by a non-selective effect and high toxicity. Conjugation of Cis-Pt with nanocarriers is thought to be one option to enable drug targeting. The aim of this study was to estimate toxic effects of the nanocomplex formed by noncovalent interaction of C60 fullerene with Cis-Pt against Lewis lung carcinoma (LLC) cells in comparison with free drug. Scanning tunneling microscopy showed that the minimum size of C60–Cis-Pt nanoparticles in aqueous colloid solution was 1.1 nm whereas that of C60 fullerene was 0.72 nm, thus confirming formation of the nanocomplex. The cytotoxic effect of C60–Cis-Pt nanocomplex against LLC cells was shown to be higher with IC50 values 3.3 and 4.5 times lower at 48 h and 72 h, respectively, as compared to the free drug. 12.5 µM Cis-Pt had no effect on LLC cell viability and morphology while C60–Cis-Pt nanocomplex in Cis-Pt-equivalent concentration substantially decreased the cell viability, impaired their shape and adhesion, inhibited migration and induced accumulation in proapoptotic subG1 phase. Apoptosis induced by the C60–Cis-Pt nanocomplex was confirmed by caspase 3/7 activation and externalization of phosphatidylserine on the outer surface of LLC cells with the double Annexin V-FITC/PI staining. We assume that C60 fullerene as a component of the C60–Cis-Pt nanocomplex promoted Cis-Pt entry and intracellular accumulation thus contributing to intensification of the drug’s toxic effect against lung cancer cells.
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Abbreviations
- Cis-Pt:
-
Cisplatin
- DMEM:
-
Dulbecco’s modified Eagle’s medium
- DMSO:
-
Dimethylsulfoxid
- FBS:
-
Fetal bovine serum
- LLC:
-
Lewis lung carcinoma
- MTT:
-
3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide
- PBS:
-
Phosphate-buffered saline
- STM:
-
Scanning tunneling microscopy
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SP is grateful to the DAAD (Germany) for support. AG also thanks the DAAD for the support (scholarship 57129429).
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This study was partially supported by STCU project no. 6256.
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Prylutska, S., Grynyuk, I., Skaterna, T. et al. Toxicity of C60 fullerene–cisplatin nanocomplex against Lewis lung carcinoma cells. Arch Toxicol 93, 1213–1226 (2019). https://doi.org/10.1007/s00204-019-02441-6
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DOI: https://doi.org/10.1007/s00204-019-02441-6