Complexation with C60 Fullerene Increases Doxorubicin Efficiency against Leukemic Cells In Vitro

Abstract

Conventional anticancer chemotherapy is limited because of severe side effects as well as a quickly evolving multidrug resistance of the tumor cells. To address this problem, we have explored a C 60 fullerene-based nanosized system as a carrier for anticancer drugs for an optimized drug delivery to leukemic cells. Here, we studied the physicochemical properties and anticancer activity of C 60 fullerene noncovalent complexes with the commonly used anticancer drug doxorubicin. C 60 -Doxorubicin complexes in a ratio 1:1 and 2:1 were characterized with UV/Vis spectrometry, dynamic light scattering, and high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The obtained analytical data indicated that the 140-nm complexes were stable and could be used for biological applications. In leukemic cell lines (CCRF-CEM, Jurkat, THP1 and Molt-16), the nanocomplexes revealed ≤ 3.5 higher cytotoxic potential in comparison with the free drug in a range of nanomolar concentrations. Also, the intracellular drug’s level evidenced C 60 fullerene considerable nanocarrier function. The results of this study indicated that C 60 fullerene-based delivery nanocomplexes had a potential value for optimization of doxorubicin efficiency against leukemic cells.

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

“…In a pioneering attempt, Evstigneev et al [57] showed a simple and fast method of noncovalent C 60 complexation with Doxorubicin in water and later in a physiological solution [59]. The strategy was applied for C 60 complexation with other chemotherapeutic drugs including Cisplatin and Landomycin A. Molecular modeling, spectroscopy, atomic-force microscopy, mass spectrometry, dynamic light, and small-angle X-ray/neutron scattering evidenced nanocomplex formation [54,56,59,60,80]. The proposed nanosystems were shown to have a higher toxicity compared with the free drugs in vitro and in vivo [54].…”

“…The enhanced toxic efficiency of Ber against leukemic cells upon its complexation with C 60 as compared with the free drug is determined by C 60 ’s ability to promote drug accumulation inside cancer cells and potentiate its toxic activity. Complexation with C 60 allowed us to enhance Ber toxicity against leukemic cells more appreciably as compared with C 60 complexation with traditional anticancer therapeutic Doxorubicin, which was followed by a less than 3.5-fold decrease of IC 50 at the same treatment duration [56]. This can be linked to the higher concentration of the safe Ber in the C 60 -containing nanocomplex (µM of Ber against nM of Doxorubicin).…”

“…Reducing the side effects of these drugs can be achieved by creating an effective targeted delivery nanosystem based, for example, on biocompatible and bioavailable C 60 [53]. It was previously shown that, when Doxorubicin or Cisplatin were immobilized on C 60 fullerene, their intracellular concentration in cancer cells was increased, leading to a pronounced antitumor effect in in vitro and in vivo systems [34,54,55,56,57,58,59,60]. Thus, one can suggest that C 60 complexation with a traditional drug is a promising nanoformulation for targeted drug delivery, substantially increasing its medico-biological effectiveness with a novel dosage form in the subsequent preclinical screening [61,62].…”

Synergy of Chemo- and Photodynamic Therapies with C60 Fullerene-Doxorubicin Nanocomplex

“…When cells were treated in the dark with the C 60 -Dox nanocomplexes at Dox equivalent concentrations, further increase of the Dox toxicity by 10–20% (Figure 5) and the decrease of its IC 50 (Table 1) were observed. These data denote C 60 ’s ability to facilitate intracellular Dox accumulation [55] and, therefore, potentiate its toxic effects.…”

“…The physicochemical properties of the C 60 -Dox nanocomplexes studied with the different analytical methods confirmed their stability and biological applicability [45,52,59,65]. Complexation with C 60 increases the intracellular Dox level and improves Dox efficiency against human leukemic and colon cancer cells [49,55].…”