TY - JOUR A1 - Radivoievych, Aleksandar A1 - Schnepel, Sophia A1 - Prylutska, Svitlana A1 - Ritter, Uwe A1 - Zolk, Oliver A1 - Frohme, Marcus A1 - Grebinyk, Anna T1 - From 2D to 3D In Vitro World: Sonodynamically-Induced Prooxidant Proapoptotic Effects of C60-Berberine Nanocomplex on Cancer Cells JF - Cancers N2 - Recently, sonodynamic therapy (SDT) has emerged as a promising non-invasive approach for treating cancer by activating sensitizers with ultrasound (US). In this context, we investigated C60 fullerene (C60) as a nanocarrier for the promising drug Berberine (Ber)—both potential aromatic sonosensitizers. The preferential mitochondrial accumulation of C60 and the proapoptotic effects of Ber also make the C60-Berberine nanocomplex (C60-Ber) a good candidate for direct induction of the intrinsic apoptotic cell death under US action. The in vitro research on C60-Ber can provide insights into novel, non-invasive cancer treatments. These findings lead to the development of targeted therapies with reduced side effects, inspire interdisciplinary collaboration, and open new avenues for drug delivery and cancer therapy research. KW - berberine KW - C60 fullerene KW - apoptosis KW - sonodynamic therapy KW - ultrasound Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-19438 VL - 16 IS - 18 ER - TY - JOUR A1 - Grebinyk, Anna A1 - Prylutska, Svitlana A1 - Grynyuk, I. A1 - Kolp, Benjamin A1 - Hurmach, V. A1 - Sliva, T. A1 - Amirkhanov, Volodymyr A1 - Trush, V. A1 - Matyshevska, Olga A1 - Slobodyanik, M. A1 - Prylutskyy, Yuriy A1 - Frohme, Marcus A1 - Ritter, Uwe T1 - C60 Fullerene Effects on Diphenyl-N-(trichloroacetyl)-amidophosphate Interaction with DNA In Silico and Its Cytotoxic Activity Against Human Leukemic Cell Line In Vitro JF - Nanoscale Research Letters N2 - 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. KW - diphenyl-N-(trichloroacetyl)-amidophosphate (HL) KW - C60 fullerene KW - leukemic CCRF-CEM cell KW - DNA KW - molecular simulation Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-10515 SN - 1556-276X VL - 2018 SP - 1 EP - 9 ER - TY - JOUR A1 - Prylutska, Svitlana A1 - Grynyuk, I. A1 - Grebinyk, Anna A1 - Hurmach, V. A1 - Shatrava, Iu. A1 - Sliva, T. A1 - Amirkhanov, Volodymyr A1 - Prylutskyy, Yuriy A1 - Matyshevska, Olga A1 - Slobodyanik, M. A1 - Frohme, Marcus A1 - Ritter, Uwe T1 - Cytotoxic Effects of Dimorfolido-N-Trichloroacetylphosphorylamide and Dimorfolido-N-Benzoylphosphorylamide in Combination with C60 Fullerene on Leukemic Cells and Docking Study of Their Interaction with DNA JF - Nanoscale Research Letters N2 - Dimorfolido-N-trichloroacetylphosphorylamide (HL1) and dimorfolido-N-benzoylphosphorylamide (HL2) as representatives of carbacylamidophosphates were synthesized and identified by the methods of IR, 1H, and 31P NMR spectroscopy. In vitro HL1 and HL2 at 1 mM concentration caused cell specific and time-dependent decrease of leukemic cell viability. Compounds caused the similar gradual decrease of Jurkat cells viability at 72 h (by 35%). HL1 had earlier and more profound toxic effect as compared to HL2 regardless on leukemic cell line. Viability of Molt-16 and CCRF-CEM cells under the action of HL1 was decreased at 24 h (by 32 and 45%, respectively) with no substantial further reducing up to 72 h. Toxic effect of HL2 was detected only at 72 h of incubation of Jurkat and Molt-16 cells (cell viability was decreased by 40 and 45%, respectively). It was shown that C60 fullerene enhanced the toxic effect of HL2 on leukemic cells. Viability of Jurkat and CCRF-CEM cells at combined action of C60 fullerene and HL2 was decreased at 72 h (by 20 and 24%, respectively) in comparison with the effect of HL2 taken separately. In silico study showed that HL1 and HL2 can interact with DNA and form complexes with DNA both separately and in combination with C60 fullerene. More stable complexes are formed when DNA interacts with HL1 or C60 + HL2 structure. Strong stacking interactions can be formed between HL2 and C60 fullerene. Differences in the types of identified bonds and ways of binding can determine distinction in cytotoxic effects of studied compounds. KW - dimorfolido-N-trichloroacetylphosphorylamide KW - dimorfolido-N-benzoylphosphorylamide KW - C60 fullerene KW - leukemic cell KW - DNA KW - computer modeling Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-9273 SN - 1556-276X VL - 12 IS - 124 ER - TY - CHAP A1 - Chepurna, Oksana A1 - Grebinyk, Anna A1 - Petrushko, Yulia A1 - Prylutska, Svitlana A1 - Grebinyk, Sergii A1 - Yashchuk, Valeriy A1 - Matyshevska, Olga A1 - Ritter, Uwe A1 - Dandekar, Thomas A1 - Frohme, Marcus A1 - Qu, Junle A1 - Ohulchanskyy, Tymish Y. T1 - LED-based portable light source for photodynamic therapy N2 - Photodynamic therapy (PDT) employs light activation of tissue-localized photosensitizer in an oxygen-dependent process which initiates oxidative stress, inflammation, and cell death. Laser systems, which are mostly used in PDT as light sources can be costly and oversized. light-emitting diodes (LEDs) equipment has a high potential to simplify technical part of phototriggered therapies and to reduce its costs. We develop the LED-based system that includes the control and irradiation units. The system provides the same power density at any irradiation point. Among the advantages of the device is a possibility to change the irradiation area and tune the irradiation dose. PDT experiments with cancer cells in vitro treated with two different photosensitizers demonstrated a possibility to use the developed LED-based system as a low-cost light source in PDT. KW - light source KW - high power single chip LED KW - photodynamic therapy Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-14778 ER - 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 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. KW - C60 fullerene KW - berberine KW - noncovalent nanocomplex KW - UV–Vis KW - DLS and AFM measurements KW - drug release KW - leukemic cell KW - uptake KW - cytotoxicity KW - apoptosis Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-12932 SN - 1999-4923 VL - 11 IS - 11 PB - MDPI ER -