TY  - JOUR
A1  - Grebinyk, Anna
A1  - Prylutska, Svitlana
A1  - Buchelnikov, Anatoliy
A1  - Tverdokhleb, Nina
A1  - Grebinyk, Sergii
A1  - Evstigneev, Maxim
A1  - Matyshevska, Olga
A1  - Cherepanov, Vsevolod
A1  - Prylutskyy, Yuriy
A1  - Yashchuk, Valeriy
A1  - Naumovets, Anton
A1  - Ritter, Uwe
A1  - Dandekar, Thomas
A1  - Frohme, Marcus
T1  - C60 fullerene as an effective nanoplatform of alkaloid Berberine delivery into leukemic cells
JF  - Pharmaceutics
N2  - 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 C\(_{60}\) binding in an aqueous solution. Complexation with C\(_{60}\) was found to promote Ber intracellular uptake. By increasing C\(_{60}\) concentration, the C\(_{60}\)-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 C\(_{60}\)-Ber nanocomplexes evidenced apoptosis induction. Thus, this study indicates that the fast and easy noncovalent complexation of alkaloid Ber with C\(_{60}\) improved its in vitro efficiency against cancer cells.
KW  - C60 fullerene
KW  - Berberine
KW  - noncovalent nanocomplex
KW  - UV–Vis
KW  - DLS and AFM measurements
KW  - drug release
KW  - leukemic cells
KW  - uptake
KW  - cytotoxicity
KW  - apoptosis
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-193216
SN  - 1999-4923
VL  - 11
IS  - 11
ER  -