Toxicity of C60 fullerene–cisplatin nanocomplex against Lewis lung carcinoma cells
| Autor: | A.G. Naumovets, Uwe Ritter, I. I. Grynyuk, Anna Grebinyk, T. D. Skaterna, Marcus Frohme, A. Senenko, Svitlana Prylutska, O. P. Matyshevska, Iryna Horak, Liudmyla Drobot, Yuriy Prylutskyy |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cisplatin Health Toxicology and Mutagenesis Lewis lung carcinoma General Medicine Phosphatidylserine 010501 environmental sciences Toxicology 01 natural sciences 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology Targeted drug delivery chemistry Annexin medicine Biophysics Viability assay Nanocarriers Cytotoxicity 0105 earth and related environmental sciences medicine.drug |
| Zdroj: | Archives of Toxicology. 93:1213-1226 |
| ISSN: | 1432-0738 0340-5761 |
| DOI: | 10.1007/s00204-019-02441-6 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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