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

  • Svitlana Prylutska
  • Iryna Grynyuk
  • Tetiana Skaterna
  • Iryna Horak
  • Anna Grebinyk
  • Liudmyla Drobot
  • Olga Matyshevska
  • Anton Senenko
  • Yuriy Prylutskyy
  • Anton Naumovets
  • Uwe Ritter
  • Marcus FrohmeEmail author
Nanotoxicology
  • 96 Downloads

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.

Keywords

C60 fullerene Cisplatin C60–Cis-Pt nanocomplex Lewis lung carcinoma cells Cytotoxicity Scanning tunneling microscopy 

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

Notes

Acknowledgements

SP is grateful to the DAAD (Germany) for support. AG also thanks the DAAD for the support (scholarship 57129429).

Funding

This study was partially supported by STCU project no. 6256.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Svitlana Prylutska
    • 1
  • Iryna Grynyuk
    • 1
  • Tetiana Skaterna
    • 2
  • Iryna Horak
    • 2
  • Anna Grebinyk
    • 1
    • 3
  • Liudmyla Drobot
    • 2
  • Olga Matyshevska
    • 1
    • 2
  • Anton Senenko
    • 4
  • Yuriy Prylutskyy
    • 1
  • Anton Naumovets
    • 4
  • Uwe Ritter
    • 5
  • Marcus Frohme
    • 3
    Email author
  1. 1.Taras Shevchenko National University of KyivKyivUkraine
  2. 2.Palladin Institute of Biochemistry, NAS of UkraineKyivUkraine
  3. 3.Technical University of Applied Sciences WildauWildauGermany
  4. 4.Institute of Physics of the NAS of UkraineKyivUkraine
  5. 5.Institute of Chemistry and BiotechnologyTechnical University of IlmenauIlmenauGermany

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