Toxicity of C60 fullerene–cisplatin nanocomplex against Lewis lung carcinoma cells

• Published in: Archives of toxicology 2019-05, Vol.93 (5), p.1213-1226
• Main Authors: Prylutska, Svitlana, Grynyuk, Iryna, Skaterna, Tetiana, Horak, Iryna, Grebinyk, Anna, Drobot, Liudmyla, Matyshevska, Olga, Senenko, Anton, Prylutskyy, Yuriy, Naumovets, Anton, Ritter, Uwe, Frohme, Marcus
• Format: Article
• Language: English
• Subjects: Accumulation; Annexin V; Anticancer properties; Apoptosis; Biomedical and Life Sciences; Biomedicine; Buckminsterfullerene; Caspase; Caspase-3; Cell viability; Chemotherapy; Cisplatin; Conjugation; Cytology; Cytotoxicity; Environmental Health; Fullerenes; Lung cancer; Lung carcinoma; Microscopy; Morphology; Nanoparticles; Nanotoxicology; Occupational Medicine/Industrial Medicine; Pharmacology/Toxicology; Phosphatidylserine; Scanning tunneling microscopy; Toxicity; Tumors
• ISSN: 0340-5761; 1432-0738
• DOI: 10.1007/s00204-019-02441-6

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 C 60 fullerene with Cis-Pt against Lewis lung carcinoma (LLC) cells in comparison with free drug. Scanning tunneling microscopy showed that the minimum size of C 60 –Cis-Pt nanoparticles in aqueous colloid solution was 1.1 nm whereas that of C 60 fullerene was 0.72 nm, thus confirming formation of the nanocomplex. The cytotoxic effect of C 60 –Cis-Pt nanocomplex against LLC cells was shown to be higher with IC 50 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 C 60 –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 C 60 –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 C 60 fullerene as a component of the C 60 –Cis-Pt nanocomplex promoted Cis-Pt entry and intracellular accumulation thus contributing to intensification of the drug’s toxic effect against lung cancer cells.