Article

C60 Fullerene as an Effective Nanoplatform of Alkaloid Berberine Delivery into Leukemic Cells

Anna GrebinykDepartment of Bioinformatics, Biocenter, University of Würzburg, Am Hubland, 97074 Würzburg, GermanySvitlana PrylutskaTaras Shevchenko National University of Kyiv, Volodymyrska 64, 01601 Kyiv, UkraineAnatoly S. BuchelnikovLaboratory of Molecular and Cell Biophysics, Sevastopol State University, 299053 Sevastopol, CrimeaNina TverdokhlebLaboratory of Molecular and Cell Biophysics, Sevastopol State University, 299053 Sevastopol, CrimeaSergii GrebinykDivision Molecular Biotechnology and Functional Genomics, Technical University of Applied Sciences Wildau, Hochschulring 1, 15745 Wildau, GermanyMaxim P. EvstigneevLaboratory of Molecular and Cell Biophysics, Sevastopol State University, 299053 Sevastopol, CrimeaOlga MatyshevskaPalladin Institute of Biochemistry, NAS of Ukraine, Leontovicha Str. 9, 01030 Kyiv, UkraineВ. В. ЧерепановInstitute of Physics, NAS of Ukraine, 46 av. Nauki, 03028 Kyiv, UkraineYu. І. PrylutskyyTaras Shevchenko National University of Kyiv, Volodymyrska 64, 01601 Kyiv, UkraineValeriy M. YashchukTaras Shevchenko National University of Kyiv, Volodymyrska 64, 01601 Kyiv, UkraineА.Г. НаумовецInstitute of Physics, NAS of Ukraine, 46 av. Nauki, 03028 Kyiv, UkraineUwe RitterInstitute of Chemistry and Biotechnology, University of Technology Ilmenau, Weimarer Straße 25 (Curiebau), 98693 Ilmenau, GermanyThomas DandekarDepartment of Bioinformatics, Biocenter, University of Würzburg, Am Hubland, 97074 Würzburg, GermanyMarcus FrohmeDivision Molecular Biotechnology and Functional Genomics, Technical University of Applied Sciences Wildau, Hochschulring 1, 15745 Wildau, Germany

2019en

ABI

Abstract

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.

Identifiers

DOI: 10.3390/pharmaceutics11110586

Citations and references

Cited by 20 references

Metrics — AkademScholar