C60 fullerene as an effective nanoplatform of alkaloid Berberine delivery into leukemic cells

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

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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Grebinyk, Anna / Prylutska, Svitlana / Buchelnikov, Anatoliy / et al: C60 fullerene as an effective nanoplatform of alkaloid Berberine delivery into leukemic cells. 2019.

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