Interaction of C 60 fullerene complexed to doxorubicin with model bilipid membranes and its uptake by HeLa cells

Prylutskyy, Yu. І.; Bychko, A.; Sokolova, V.; Prylutska, Svitlana; Evstigneev, Maxim P.; Rybal’chenko, V. K.; Epple, Matthias; Scharff, P.

doi:10.1016/j.msec.2015.10.049

Cited by 34 publications

(13 citation statements)

References 31 publications

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“…It is important to note that in the case of Dextran-PNIPAM+Dox NPs, the results for CLSM almost are no different from those we obtained earlier for pure Dox at 3 hours of incubation with HeLa cells. 33 This again confirms the fact that the water-soluble Dextran-PNIPAM copolymer acts as the Dox molecules transporter into cells, actively releasing them to the intracellular space at physiological temperature. 12 Thus, one may conclude that the Dextran-PNIPAM+Dox NPs can be used for further pre-clinical trials.…”

Section: Resultssupporting

confidence: 63%

In vitro study of the anticancer activity of various doxorubicin-containing dispersions

et al. 2018

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Introduction: The aim of this research was to study the impact of various doxorubicin (Dox)-containing nanofluids, e.g. singlewalled carbon nanotube (SWCNT)+Dox, graphene oxide (GO)+Dox and DextranPNIPAM (copolymer)+Dox mixtures on HeLa cells (human transformed cervix epithelial cells, as a model for cancer cells) depending on their concentration. Methods: Structural analysis of GO+Dox complex was accomplished using Hartree-Fock level of theory in 6-31G** basis set in Gaussian. Dynamic light scattering (DLS), zeta-potential, scanning electron microscopy and confocal laser scanning microscopy were used. The cell viability was analyzed by the MTT assay. Results: The viability of HeLa cells was studied with the MTT assay after the incubation with various Dox-containing dispersions depending on their concentration. The size of the particles was determined by DLS. The morphology of the nanoparticles (NPs) was studied by scanning electron microscopy and their uptake into cells was visualized by confocal laser scanning microscopy. It was found that the Dextran-PNIPAM+Dox nanofluid in contrast to Dox alone showed higher toxicity towards HeLa cells up to 80% after 24 hours of incubation, whereas the SWCNT+Dox and GO+Dox nanofluids at the same concentrations protected cells from Dox. Conclusion: The importance of Dextran-PNIPAM copolymer as a universal platform for drug delivery was established, and the huge potential of Dextran-PNIPAM+Dox NPs as novel anticancer agents was noted. Based on the in vitro study of the SWCNT+Dox and GO+Dox nanofluids, it was concluded that SWCNT and GO NPs can be effective cytoprotectors against the highly toxic drugs.

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Section: Resultssupporting

confidence: 63%

In vitro study of the anticancer activity of various doxorubicin-containing dispersions

et al. 2018

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“…C 60 is a highly efficient “free radical sponge” [32] due to pronounced electrophilicity (the ability to accept up to six electrons). Wang et al [33] reported that C 60 and its derivatives efficiently prevent peroxidation and membrane breakdown triggered by free radical species and are more effective in inhibiting lipid peroxidation than a natural antioxidant vitamin E. C 60 is a hydrophobic molecule able to penetrate into both the lipid bilayer and the cell membranes [34,35]. Pristine C 60 [36,37] and its water-soluble derivative [38] were found to be accumulated in mitochondria.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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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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“…Nitrobenzyl phosphoramide mustards were shown to permeate across cell membranes and to be localized in mitochondria of NTR + mammalian cells [ 10 ]. It is not excluded that C 60 fullerene, which is able to penetrate the membrane of the cancer cell due to passive diffusion or endocytosis [ 28 , 30 , 32 ] with accumulation in the nucleus and mitochondria [ 30 , 32 , 33 ], could be a transporter of small antitumor molecules [ 38 – 40 ].…”

Section: Resultsmentioning

confidence: 99%

C60 Fullerene Effects on Diphenyl-N-(trichloroacetyl)-amidophosphate Interaction with DNA In Silico and Its Cytotoxic Activity Against Human Leukemic Cell Line In Vitro

et al. 2018

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New representative of carbacylamidophosphates - diphenyl-N-(trichloroacetyl)-amidophosphate (HL), which contains two phenoxy substituents near the phosphoryl group, was synthesized, identified by elemental analysis and IR and NMR spectroscopy, and tested as a cytotoxic agent itself and in combination with C60 fullerene.According to molecular simulation results, C60 fullerene and HL could interact with DNA and form a rigid complex stabilized by stacking interactions of HL phenyl groups with C60 fullerene and DNA G nucleotide, as well as by interactions of HL CCl3 group by ion-π bonds with C60 molecule and by electrostatic bonds with DNA G nucleotide.With the use of MTT test, the cytotoxic activity of HL against human leukemic CCRF-CM cells with IC50 value detected at 10 μM concentration at 72 h of cells treatment was shown. Under combined action of 16 μM C60 fullerene and HL, the value of IC50 was detected at lower 5 μM HL concentration and at earlier 48 h period of incubation, besides the cytotoxic effect of HL was observed at a low 2.5 μM concentration at which HL by itself had no influence on cell viability. Binding of C60 fullerene and HL with minor DNA groove with formation of a stable complex is assumed to be one of the possible reasons of their synergistic inhibition of CCRF-CЕM cells proliferation.Application of C60 fullerene in combination with 2.5 μM HL was shown to have no harmful effect on structural stability of blood erythrocytes membrane. Thus, combined action of C60 fullerene and HL in a low concentration potentiated HL cytotoxic effect against human leukemic cells and was not followed by hemolytic effect.

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Interaction of C 60 fullerene complexed to doxorubicin with model bilipid membranes and its uptake by HeLa cells

Cited by 34 publications

References 31 publications

In vitro study of the anticancer activity of various doxorubicin-containing dispersions

In vitro study of the anticancer activity of various doxorubicin-containing dispersions

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

C60 Fullerene Effects on Diphenyl-N-(trichloroacetyl)-amidophosphate Interaction with DNA In Silico and Its Cytotoxic Activity Against Human Leukemic Cell Line In Vitro

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