Pharmaceutics (Nov 2019)

C<sub>60</sub> Fullerene as an Effective Nanoplatform of Alkaloid Berberine Delivery into Leukemic Cells

  • Anna Grebinyk,
  • Svitlana Prylutska,
  • Anatoliy Buchelnikov,
  • Nina Tverdokhleb,
  • Sergii Grebinyk,
  • Maxim Evstigneev,
  • Olga Matyshevska,
  • Vsevolod Cherepanov,
  • Yuriy Prylutskyy,
  • Valeriy Yashchuk,
  • Anton Naumovets,
  • Uwe Ritter,
  • Thomas Dandekar,
  • Marcus Frohme

DOI
https://doi.org/10.3390/pharmaceutics11110586
Journal volume & issue
Vol. 11, no. 11
p. 586

Abstract

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A herbal alkaloid Berberine (Ber), used for centuries in Ayurvedic, Chinese, Middle-Eastern, and native American folk medicines, is nowadays proved to function as a safe anticancer agent. Yet, its poor water solubility, stability, and bioavailability hinder clinical application. In this study, we have explored a nanosized carbon nanoparticle—C60 fullerene (C60)—for optimized Ber delivery into leukemic cells. Water dispersions of noncovalent C60-Ber nanocomplexes in the 1:2, 1:1, and 2:1 molar ratios were prepared. UV−Vis spectroscopy, dynamic light scattering (DLS), and atomic force microscopy (AFM) evidenced a complexation of the Ber cation with the negatively charged C60 molecule. The computer simulation showed that π-stacking dominates in Ber and C60 binding in an aqueous solution. Complexation with C60 was found to promote Ber intracellular uptake. By increasing C60 concentration, the C60-Ber nanocomplexes exhibited higher antiproliferative potential towards CCRF-CEM cells, in accordance with the following order: free Ber < 1:2 < 1:1 < 2:1 (the most toxic). The activation of caspase 3/7 and accumulation in the sub-G1 phase of CCRF-CEM cells treated with C60-Ber nanocomplexes evidenced apoptosis induction. Thus, this study indicates that the fast and easy noncovalent complexation of alkaloid Ber with C60 improved its in vitro efficiency against cancer cells.

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