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

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.

Recent Advances in Berberine Inspired Anticancer Approaches: From Drug Combination to Novel Formulation Technology and Derivatization

“…It is worth reiterating that poor intestinal absorption, extensive efflux by the action of P-gc and extensive degradation account to the rather poor bioavailability/pharmacokinetics profile of berberine. The various formulation approaches specifically designed to tackle this problem and improve berberine's anticancer efficacy are shown in Table 2 [106][107][108][109][110][111][112][113][114][115][116][117][118][119][120][121][122][123]. These include nanoparticles of various sizes and surface charges with some specifically targeting subcellular organelles, such as the mitochondria.…”

“…Grebinyk et al [106] Anionic and cationic vitamin E-TPGS mixed polymeric phospholipid micellar vehicles Lipid-based nanocarriers, amphiphilic mixed micelles composed of polymeric phospholipid conjugates and PEG-succinate ester of tocopherol.…”

Identification of potential descriptors of water-soluble fullerene derivatives responsible for antitumor effects on lung cancer cells via QSAR analysis

“…Fullerenes and their derivatives are promising nanomaterials with a wide range of biomedical applications. For example, fullerene C 60 and C 70 derivatives can act as anti-HIV drugs [35] , cancer cell inhibitors [36] , DNA photocleavage [37] , superconducting materials [38] , radionuclide chelating agents [39] , drug delivery carriers [40] , [41] , [42] , and strong antioxidants [43] , [44] , [45] , [46] . The membrane transportation of fullerenes and their derivatives has been actively investigated during the past decade, and distinct penetration through lipid bilayers of cell membranes was revealed [47] , [48] , [49] , [50] .…”

The electronic states and vibronic absorption spectrum of berberine in aqueous solution

“…BER can efficiently bind to nucleic acids [17–30] and is used for photodynamic therapy of tumors (cleavage of 1 O 2 singlet oxygen from the BER molecule under the action of UV laser radiation) [31–33]. Fullerene molecules can be used to enhance the action and delivery of BER to cancer cells [34,35].…”