TY - JOUR A1 - Radivoievych, Aleksandar A1 - Kolp, Benjamin A1 - Grebinyk, Sergii A1 - Prylutska, Svitlana A1 - Ritter, Uwe A1 - Zolk, Oliver A1 - Glökler, Jörn A1 - Frohme, Marcus A1 - Grebinyk, Anna T1 - Silent Death by Sound: C60 Fullerene Sonodynamic Treatment of Cancer Cells JF - International Journal of Molecular Sciences N2 - The acoustic pressure waves of ultrasound (US) not only penetrate biological tissues deeper than light, but they also generate light emission, termed sonoluminescence. This promoted the idea of its use as an alternative energy source for photosensitizer excitation. Pristine C60 fullerene (C60), an excellent photosensitizer, was explored in the frame of cancer sonodynamic therapy (SDT). For that purpose, we analyzed C60 effects on human cervix carcinoma HeLa cells in combination with a low-intensity US treatment. The time-dependent accumulation of C60 in HeLa cells reached its maximum at 24 h (800 ± 66 ng/106 cells). Half of extranuclear C60 is localized within mitochondria. The efficiency of the C60 nanostructure’s sonoexcitation with 1 MHz US was tested with cell-based assays. A significant proapoptotic sonotoxic effect of C60 was found for HeLa cells. C60′s ability to induce apoptosis of carcinoma cells after sonoexcitation with US provides a promising novel approach for cancer treatment. KW - ultrasound KW - C60 fullerene KW - sonodynamic therapy KW - HeLa cells KW - apoptosis Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-16877 SN - 1422-0067 VL - 24 IS - 2 PB - MDPI 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 - TY - JOUR A1 - Grebinyk, Anna A1 - Prylutska, Svitlana A1 - Chepurna, Oksana A1 - Grebinyk, Sergii A1 - Prylutskyy, Yuriy A1 - Ritter, Uwe A1 - Ohulchanskyy, Tymish Y. A1 - Matyshevska, Olga A1 - Dandekar, Thomas A1 - Frohme, Marcus T1 - Synergy of Chemo- and Photodynamic Therapies with C60 Fullerene-Doxorubicin Nanocomplex JF - Nanomaterials N2 - A nanosized drug complex was explored to improve the efficiency of cancer chemotherapy, complementing it with nanodelivery and photodynamic therapy. For this, nanomolar amounts of a non-covalent nanocomplex of Doxorubicin (Dox) with carbon nanoparticle C60 fullerene (C60) were applied in 1:1 and 2:1 molar ratio, exploiting C60 both as a drug-carrier and as a photosensitizer. The fluorescence microscopy analysis of human leukemic CCRF-CEM cells, in vitro cancer model, treated with nanocomplexes showed Dox’s nuclear and C60’s extranuclear localization. It gave an opportunity to realize a double hit strategy against cancer cells based on Dox’s antiproliferative activity and C60’s photoinduced pro-oxidant activity. When cells were treated with 2:1 C60-Dox and irradiated at 405 nm the high cytotoxicity of photo-irradiated C60-Dox enabled a nanomolar concentration of Dox and C60 to efficiently kill cancer cells in vitro. The high pro-oxidant and pro-apoptotic efficiency decreased IC50 16, 9 and 7 × 103-fold, if compared with the action of Dox, non-irradiated nanocomplex, and C60’s photodynamic effect, correspondingly. Hereafter, a strong synergy of therapy arising from the combination of C60-mediated Dox delivery and C60 photoexcitation was revealed. Our data indicate that a combination of chemo- and photodynamic therapies with C60-Dox nanoformulation provides a promising synergetic approach for cancer treatment. KW - photodynamic chemotherapy KW - synergistic effect KW - C60 fullerene KW - doxorubicin KW - nanocomplex KW - leukemic cell KW - apoptosis Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-12940 SN - 2079-4991 VL - 9 IS - 11 PB - MDPI ER - TY - JOUR A1 - Radivoievych, Aleksandar A1 - Prylutska, Svitlana A1 - Zolk, Oliver A1 - Ritter, Uwe A1 - Frohme, Marcus A1 - Grebinyk, Anna T1 - Comparison of Sonodynamic Treatment Set-Ups for Cancer Cells with Organic Sonosensitizers and Nanosonosensitizers JF - Pharmaceutics N2 - Cancer sonodynamic therapy (SDT) is the therapeutic strategy of a high-frequency ultrasound (US) combined with a special sonosensitizer that becomes cytotoxic upon US exposure. The growing number of newly discovered sonosensitizers and custom US in vitro treatment solutions push the SDT field into a need for systemic studies and reproducible in vitro experimental set-ups. In the current research, we aimed to compare two of the most used and suitable SDT in vitro set-ups—“sealed well” and “transducer in well”—in one systematic study. We assessed US pressure, intensity, and temperature distribution in wells under US irradiation. Treatment efficacy was evaluated for both set-ups towards cancer cell lines of different origins, treated with two promising sonosensitizer candidates—carbon nanoparticle C60 fullerene (C60) and herbal alkaloid berberine. C60 was found to exhibit higher sonotoxicity toward cancer cells than berberine. The higher efficacy of sonodynamic treatment with a “transducer in well” set-up than a “sealed well” set-up underlined its promising application for SDT in vitro studies. The “transducer in well” set-up is recommended for in vitro US treatment investigations based on its US-field homogeneity and pronounced cellular effects. Moreover, SDT with C60 and berberine could be exploited as a promising combinative approach for cancer treatment. KW - ultrasound KW - C60 fullerene KW - berberine KW - sonodynamic therapy KW - apoptosis Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-18223 SN - 1999-4923 VL - 15 IS - 11 PB - MDPI ER - TY - JOUR A1 - Grebinyk, Anna A1 - Yashchuk, Valeriy A1 - Bashmakova, Nataliya A1 - Gryn, Dmytro A1 - Hagemann, Tobias A1 - Naumenko, Antonina A1 - Kutsevol, Nataliya A1 - Dandekar, Thomas A1 - Frohme, Marcus T1 - A New Triple System DNA-Nanosilver-Berberine for Cancer Therapy JF - Applied Nanoscience N2 - The isoquinoline quaternary alkaloid Berberine possesses a variety of pharmacological properties that suggests its promising application for an anticancer delivery system design utilizing its ability to intercalate DNA.In the current work we have investigated the effects of Berberine on the human T-cell leukemia cell line in vitro.Fluorescent microscopy of leukemic cells revealed Berberine nuclear localization. The results showed that Berberine inhibited leukemic cell growth in a time-and dose-dependent manner, that was associated with reactive oxygen species production intensification and caspase 3/7 activity increase with followed apoptosis induction.Berberine was used as a toxic and phototoxic agent for triple system synthesis along with DNA as a carrier and nanosilver as a plasmonic accelerator of Berberine electronic transitions and high energy emission absorbent centers.The proposed method allows to obtain the complex of DNA with Berberine molecules and silver nanopoarticles. The optical properties of free components as well as their various combinations, including the final triple system DNA-Nanosilver-Berberine, were investigated. Obtained results support the possibility to use the triple system DNA-Nanosilver-Berberine as an alternative therapeutic agent for cancer treatment. KW - berberine KW - apoptosis KW - nanosilver KW - DNA delivery system Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-10628 SN - 2190-5517 ER -