@article{RadivoievychKolpGrebinyketal.2023, author = {Radivoievych, Aleksandar and Kolp, Benjamin and Grebinyk, Sergii and Prylutska, Svitlana and Ritter, Uwe and Zolk, Oliver and Gl{\"o}kler, J{\"o}rn and Frohme, Marcus and Grebinyk, Anna}, title = {Silent Death by Sound: C60 Fullerene Sonodynamic Treatment of Cancer Cells}, series = {International Journal of Molecular Sciences}, volume = {24}, journal = {International Journal of Molecular Sciences}, number = {2}, publisher = {MDPI}, issn = {1422-0067}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-16877}, year = {2023}, abstract = {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.}, language = {en} } @article{GrebinykGrebinykPrylutskaetal.2018, author = {Grebinyk, Anna and Grebinyk, Sergii and Prylutska, Svitlana and Ritter, Uwe and Matyshevska, Olga and Dandekar, Thomas and Frohme, Marcus}, title = {HPLC-ESI-MS method for C60 fullerene mitochondrial content quantification}, series = {Data in Brief}, volume = {19}, journal = {Data in Brief}, issn = {2352-3409}, doi = {10.1016/j.dib.2018.06.089}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-10368}, pages = {2047 -- 2052}, year = {2018}, abstract = {The presented dataset describes the quantification of carbon nanoparticle C60 fullerene accumulated in mitochondria of human leukemic cells treated with nanostructure. Firstly, the high performance liquid chromatography-electro spray ionization-mass spectrometry (HPLC-ESI-MS) method was developed for quantitative analysis of pristine C60 fullerene. Then, human leukemic cells were incubated with C60 fullerene, homogenized and subjected to the differential centrifugation to retrieve mitochondrial fraction. The C60 fullerene content was quantified by HPLC-ESI-MS in extracts of cellular fractions. This data article refers to the research article "C60 Fullerene Accumulation in Human Leukemic Cells and Perspectives of LED-mediated Photodynamic Therapy" by Grebinyk et al.}, language = {en} } @article{GrebinykGrebinykPrylutskaetal.2018, author = {Grebinyk, Anna and Grebinyk, Sergii and Prylutska, Svitlana and Ritter, Uwe and Matyshevska, Olga and Dandekar, Thomas and Frohme, Marcus}, title = {C60 fullerene accumulation in human leukemic cells and perspectives of LED-mediated photodynamic therapy}, series = {Free Radical Biology and Medicine}, volume = {124}, journal = {Free Radical Biology and Medicine}, issn = {1873-4596}, doi = {10.1016/j.freeradbiomed.2018.06.022}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-10588}, pages = {319 -- 327}, year = {2018}, abstract = {Recent progress in nanobiotechnology has attracted interest to a biomedical application of the carbon nanostructure C60 fullerene since it possesses a unique structure and versatile biological activity. C60 fullerene potential application in the frame of cancer photodynamic therapy (PDT) relies on rapid development of new light sources as well as on better understanding of the fullerene interaction with cells. The aim of this study was to analyze C60 fullerene effects on human leukemic cells (CCRF-CEM) in combination with high power single chip light-emitting diodes (LEDs) light irradiation of different wavelengths: ultraviolet (UV, 365 nm), violet (405 nm), green (515 nm) and red (632 nm). The time-dependent accumulation of fullerene C60 in CCRF-CEM cells up to 250 ng/106 cells at 24 h with predominant localization within mitochondria was demonstrated with immunocytochemical staining and liquid chromatography mass spectrometry. In a cell viability assay we studied photoexcitation of the accumulated C60 nanostructures with ultraviolet or violet LEDs and could prove that significant phototoxic effects did arise. A less pronounced C60 fullerene phototoxic effect was observed after irradiation with green, and no effect was detected with red light. A C60 fullerene photoactivation with violet light induced substantial ROS generation and apoptotic cell death, confirmed by caspase3/7 activation and plasma membrane phosphatidylserine externalization. Our work proved C60 fullerene ability to induce apoptosis of leukemic cells after photoexcitation with high power single chip 405 nm LED as a light source. This underlined the potential for application of C60 nanostructure as a photosensitizer for anticancer therapy.}, language = {en} } @inproceedings{ChepurnaGrebinykPetrushkoetal.2019, author = {Chepurna, Oksana and Grebinyk, Anna and Petrushko, Yulia and Prylutska, Svitlana and Grebinyk, Sergii and Yashchuk, Valeriy and Matyshevska, Olga and Ritter, Uwe and Dandekar, Thomas and Frohme, Marcus and Qu, Junle and Ohulchanskyy, Tymish Y.}, title = {LED-based portable light source for photodynamic therapy}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-14778}, year = {2019}, abstract = {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.}, language = {en} } @article{GrebinykPrylutskaBuchelnikovetal.2019, author = {Grebinyk, Anna and Prylutska, Svitlana and Buchelnikov, Anatoliy and Tverdokhleb, Nina and Grebinyk, Sergii and Evstigneev, Maxim and Matyshevska, Olga and Cherepanov, Vsevolod and Prylutskyy, Yuriy and Yashchuk, Valeriy and Naumovets, Anton and Ritter, Uwe and Dandekar, Thomas and Frohme, Marcus}, title = {C60 Fullerene as an Effective Nanoplatform of Alkaloid Berberine Delivery into Leukemic Cells}, series = {Pharmaceutics}, volume = {11}, journal = {Pharmaceutics}, number = {11}, publisher = {MDPI}, issn = {1999-4923}, doi = {10.3390/pharmaceutics11110586}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-12932}, year = {2019}, 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.}, language = {en} } @article{GrebinykPrylutskaChepurnaetal.2019, author = {Grebinyk, Anna and Prylutska, Svitlana and Chepurna, Oksana and Grebinyk, Sergii and Prylutskyy, Yuriy and Ritter, Uwe and Ohulchanskyy, Tymish Y. and Matyshevska, Olga and Dandekar, Thomas and Frohme, Marcus}, title = {Synergy of Chemo- and Photodynamic Therapies with C60 Fullerene-Doxorubicin Nanocomplex}, series = {Nanomaterials}, volume = {9}, journal = {Nanomaterials}, number = {11}, publisher = {MDPI}, issn = {2079-4991}, doi = {10.3390/nano9111540}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-12940}, year = {2019}, abstract = {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.}, language = {en} } @article{GrebinykPrylutskaGrebinyketal.2021, author = {Grebinyk, Anna and Prylutska, Svitlana and Grebinyk, Sergii and Evstigneev, Maxim and Krysiuk, Iryna and Skaterna, Tetiana and Horak, Iryna and Sun, Yanfang and Drobot, Liudmyla and Matyshevska, Olga and Prylutskyy, Yuriy and Ritter, Uwe and Frohme, Marcus}, title = {Antitumor efficiency of the natural alkaloid berberine complexed with C60 fullerene in Lewis lung carcinoma in vitro and in vivo}, series = {Cancer Nanotechnology}, volume = {12}, journal = {Cancer Nanotechnology}, publisher = {BioMed Central}, issn = {1868-6966}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-14749}, pages = {24}, year = {2021}, abstract = {Background Berberine (Ber) is a herbal alkaloid with pharmacological activity in general and a high anticancer potency in particular. However, due to its low bioavailability, the difficulty in reaching a target and choosing the right dose, there is a need to improve approaches of Ber use in anticancer therapy. In this study, Ber, noncovalently bound to a carbon nanostructure C60 fullerene (C60) at various molar ratios of the components, was explored against Lewis lung carcinoma (LLC). Methods C60-Ber noncovalent nanocomplexes were synthesized in 1:2, 1:1 and 2:1 molar ratios. Ber release from the nanocomplexes was studied after prolonged incubation at different pH with the liquid chromatography-mass spectrometry analysis of free Ber content. Biological effects of the free and C60-complaxated Ber were studied in vitro towards LLC cells with phase-contrast and fluorescence microscopy, flow cytometry, MTT reduction, caspase activity and wound closure assays. The treatment with C60-Ber nanocomplex was evaluated in vivo with the LLC-tumored C57Bl mice. The mice body weight, tumor size, tumor weight and tumor weight index were assessed for four groups, treated with saline, 15 mg C60/kg, 7.5 mg Ber/kg or 2:1 C60-Ber nanocomplex (15 mg C60/kg, 7.5 mg Ber/kg). Results Ber release from C60-Ber nanocomplexes was promoted with medium acidification. LLC cells treatment with C60-Ber nanocomplexes was followed by enhanced Ber intracellular uptake as compared to free Ber. The cytotoxicity of the studied agents followed the order: free Ber < 1:2 < 1:1 < 2:1 C60-Ber nanocomplex. The potency of cytotoxic effect of 2:1 C60-Ber nanocomplex was confirmed by 21.3-fold decrease of IC50 value (0.8 ± 0.3 µM) compared to IC50 for free Ber (17 ± 2 µM). C60-Ber nanocomplexes induced caspase 3/7 activation and suppressed the migration activity of LLC cells. The therapeutic potency of 2:1 C60-Ber nanocomplex was confirmed in a mouse model of LLC. The tumor growth in the group treated with 2:1 C60-Ber nanocomplex is suppressed by approximately 50\% at the end of experiment, while in the tumor-bearing group treated with free Ber no therapeutic effect was detected. Conclusions This study indicates that complexation of natural alkaloid Ber with C60 may be a novel therapeutic strategy against lung carcinoma.}, language = {en} } @article{GrebinykPrylutskaGrebinyketal.2022, author = {Grebinyk, Anna and Prylutska, Svitlana and Grebinyk, Sergii and Ponomarenko, Stanislav and Virych, Pavlo and Chumachenko, Vasyl and Kutsevol, Nataliya and Prylutskyy, Yuriy and Ritter, Uwe and Frohme, Marcus}, title = {Drug delivery with a pH-sensitive star-like dextran-graft polyacrylamide copolymer}, series = {Nanoscale Advances}, volume = {4}, journal = {Nanoscale Advances}, number = {23}, publisher = {Royal Society of Chemistry (RSC)}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-16749}, pages = {5077 -- 5088}, year = {2022}, abstract = {The development of precision cancer medicine relies on novel formulation strategies for targeted drug delivery to increase the therapeutic outcome. Biocompatible polymer nanoparticles, namely dextran-graft-polyacrylamide (D-g-PAA) copolymers, represent one of the innovative non-invasive approaches for drug delivery applications in cancer therapy. In this study, the star-like D-g-PAA copolymer in anionic form (D-g-PAAan) was developed for pH-triggered targeted drug delivery of the common chemotherapeutic drugs - doxorubicin (Dox) and cisplatin (Cis). The initial D-g-PAA copolymer was synthesized by the radical graft polymerization method, and then alkaline-hydrolyzed to get this polymer in anionic form for further use for drug encapsulation. The acidification of the buffer promoted the release of loaded drugs. D-g-PAAan nanoparticles increased the toxic potential of the drugs against human and mouse lung carcinoma cells (A549 and LLC), but not against normal human lung cells (HEL299). The drug-loaded D-g-PAAan-nanoparticles promoted further oxidative stress and apoptosis induction in LLC cells. D-g-PAAan-nanoparticles improved Dox accumulation and drugs' toxicity in a 3D LLC multi-cellular spheroid model. The data obtained indicate that the strategy of chemotherapeutic drug encapsulation within the branched D-g-PAAan nanoparticle allows not only to realize pH-triggered drug release but also to potentiate its cytotoxic, prooxidant and proapoptotic effects against lung carcinoma cells.}, language = {en} } @article{GrebinykPrylutskaGrebinyketal.2019, author = {Grebinyk, Anna and Prylutska, Svitlana and Grebinyk, Sergii and Prylutskyy, Yuriy and Ritter, Uwe and Matyshevska, Olga and Dandekar, Thomas and Frohme, Marcus}, title = {Complexation with C60 Fullerene Increases Doxorubicin Efficiency against Leukemic Cells In Vitro}, series = {Nanoscale Research Letters}, volume = {14}, journal = {Nanoscale Research Letters}, issn = {1556-276X}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-10966}, year = {2019}, 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 C60 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 C60 fullerene noncovalent complexes with the commonly used anticancer drug doxorubicin. C60-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 C60 fullerene considerable nanocarrier function. The results of this study indicated that C60 fullerene-based delivery nanocomplexes had a potential value for optimization of doxorubicin efficiency against leukemic cells.}, language = {en} } @article{GrebinykPrylutskaGrebinyketal.2019, author = {Grebinyk, Anna and Prylutska, Svitlana and Grebinyk, Sergii and Prylutskyy, Yuriy and Ritter, Uwe and Matyshevska, Olga and Dandekar, Thomas and Frohme, Marcus}, title = {Complexation with C60 Fullerene Increases Doxorubicin Efficiency against Leukemic Cells In Vitro}, series = {Nanoscale Research Letters}, volume = {14}, journal = {Nanoscale Research Letters}, issn = {1556-276X}, doi = {10.1186/s11671-019-2894-1}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-11415}, year = {2019}, 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 C60 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 C60 fullerene noncovalent complexes with the commonly used anticancer drug doxorubicin. C60-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 C60 fullerene considerable nanocarrier function. The results of this study indicated that C60 fullerene-based delivery nanocomplexes had a potential value for optimization of doxorubicin efficiency against leukemic cells.}, language = {en} } @phdthesis{Grebinyk2021, author = {Grebinyk, Anna}, title = {Synergistic Chemo- and Photodynamic Treatment of Cancer Cells with C60 Fullerene Nanocomplexes}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-14137}, school = {Technische Hochschule Wildau}, year = {2021}, abstract = {Recent progress in nanotechnology has attracted interest to a biomedical application of the carbon nanoparticle C60 fullerene (C60) due to its unique structure and versatile biological activity. In the current study the dual functionality of C60 as a photosensitizer and a drug nanocarrier was exploited to improve the efficiency of chemotherapeutic drugs towards human leukemic cells. Pristine C60 demonstrated time-dependent accumulation with predominant mitochondrial localization in leukemic cells. C60's effects on leukemic cells irradiated with high power single chip LEDs of different wavelengths were assessed to find out the most effective photoexcitation conditions. A C60-based noncovalent nanosized system as a carrier for an optimized drug delivery to the cells was evaluated in accordance to its physicochemical properties and toxic effects. Finally, nanomolar amounts of C60-drug nanocomplexes in 1:1 and 2:1 molar ratios were explored to improve the efficiency of cell treatment, complementing it with photodynamic approach. A proposed treatment strategy was developed for C60 nanocomplexes with the common chemotherapeutic drug Doxorubicin, whose intracellular accumulation and localization, cytotoxicity and mechanism of action were investigated. The developed strategy was revealed to be transferable to an alternative potent anticancer drug - the herbal alkaloid Berberine. Hereafter, a strong synergy of treatments arising from the combination of C60-mediated drug delivery and C60 photoexcitation was revealed. Presented data indicate that a combination of chemo- and photodynamic treatments with C60-drug nanoformulations could provide a promising synergetic approach for cancer treatment.}, subject = {cancer}, language = {en} } @article{RadivoievychPrylutskaZolketal.2023, author = {Radivoievych, Aleksandar and Prylutska, Svitlana and Zolk, Oliver and Ritter, Uwe and Frohme, Marcus and Grebinyk, Anna}, title = {Comparison of Sonodynamic Treatment Set-Ups for Cancer Cells with Organic Sonosensitizers and Nanosonosensitizers}, series = {Pharmaceutics}, volume = {15}, journal = {Pharmaceutics}, number = {11}, publisher = {MDPI}, issn = {1999-4923}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-18223}, year = {2023}, abstract = {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.}, language = {en} } @inproceedings{LiAmirkhanyanAftabetal.2024, author = {Li, X.-K. and Amirkhanyan, Z. and Aftab, N. and Boonpornprasert, Prach and Dmytriiev, D. and Frohme, Marcus and Georgiev, G. and Grebinyk, Anna and Gross, M. and Hoffmann, A. and Komar, Yuliia and Krasilnikov, M. and Loisch, G. and Oppelt, A. and Richard, C. and Riemer, F. and Philipp, S. and Schmitz, M. and M{\"u}ller, F. and Obier, F. and Vashchenko, Grygorii and Worm, S. and Stephan, F.}, title = {Overview of FLASHlab@PITZ: the new R\&D platform for FLASH radiation therapy and radiation biology}, series = {Journal of Physics: Conference Series, Volume 2687, Applications of Accelerators, Technology Transfer and Industrial Relations and Outreach}, volume = {2687}, booktitle = {Journal of Physics: Conference Series, Volume 2687, Applications of Accelerators, Technology Transfer and Industrial Relations and Outreach}, publisher = {Institute of Physics Publishing (IOP)}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-18474}, year = {2024}, abstract = {An R\&D platform for electron FLASH radiation therapy and radiation biology is being prepared at the Photo Injector Test facility at DESY in Zeuthen (FLASHlab@PITZ). This platform is based on the unique beam parameters available at PITZ: ps scale electron bunches of up to 22 MeV with up to 5 nC bunch charge at MHz bunch repetition rate in bunch trains of up to 1 ms in length repeating at 1 to 10 Hz. It works together with the Technical University of Applied Sciences Wildau (TH Wildau) as partner in close vicinity for the biological resources. A startup beamline has been installed to allow dosimetry studies and irradiation experiments on chemical, biochemical and biological samples after a 60-degree dispersive arm. The measured dose and dose rates under different beam conditions and first experimental results will be reported in this paper. In addition, a dedicated beamline for FLASHlab@PITZhas been designed for better control of the high brightness electron beams. This includes a dogleg to translate the beam and a 2D kicker system to scan the tiny beam focused by quadrupoles across the samples within less than 1 ms. Simulation studies will be presented to demonstrate the extremely flexible dose parameters with various irradiation options for electron FLASH radiation therapy and radiation biology studies.}, language = {en} } @article{GrebinykYashchukBashmakovaetal.2019, author = {Grebinyk, Anna and Yashchuk, Valeriy and Bashmakova, Nataliya and Gryn, Dmytro and Hagemann, Tobias and Naumenko, Antonina and Kutsevol, Nataliya and Dandekar, Thomas and Frohme, Marcus}, title = {A new triple system DNA-Nanosilver-Berberine for cancer therapy}, series = {Applied Nanoscience}, volume = {9}, journal = {Applied Nanoscience}, publisher = {Springer}, issn = {2190-5517}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-16105}, pages = {945 -- 956}, year = {2019}, abstract = {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 nanoparticles. 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.}, language = {en} } @article{PrylutskaGrebinykPonomarenkoetal.2024, author = {Prylutska, Svitlana and Grebinyk, Anna and Ponomarenko, Stanislav and G{\"o}vem, Defne and Chumachenko, Vasyl and Kutsevol, Nataliya and Petrovsky, Mykola and Ritter, Uwe and Frohme, Marcus and Piosik, Jacek and Prylutskyy, Yuriy}, title = {Toxicity of Water-Soluble D-g-PNIPAM Polymers in a Complex with Chemotherapy Drugs and Mechanism of Their Action In Vitro}, series = {International Journal of Molecular Sciences}, volume = {25}, journal = {International Journal of Molecular Sciences}, number = {5}, publisher = {MDPI}, issn = {1422-0067}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-18790}, year = {2024}, abstract = {The application of a biocompatible polymer nanocarrier can provide target delivery to tumor tissues, improved pharmacokinetics, controlled drug release, etc. Therefore, the proposed strategy was to use the water-soluble star-like copolymers with a Dextran core and Poly(N-isopropylacrylamide) grafts (D-g-PNIPAM) for conjugation with the widely used chemotherapy drugs in oncology-Cisplatin (Cis-Pt) and Doxorubicin (Dox). The molecular characteristics of the copolymer were received using size-exclusion chromatography. The physicochemical characterization of the D-g-PNIPAM-Cis-Pt (or Dox) nanosystem was conducted using dynamic light scattering and FTIR spectroscopy. Using traditional biochemical methods, a comparative analysis of the enhancement of the cytotoxic effect of free Cis-Pt and Dox in combination with D-g-PNIPAM copolymers was performed in cancer cells of the Lewis lung carcinoma line, which are both sensitive and resistant to Dox; in addition, the mechanism of their action in vitro was evaluated.}, language = {en} } @article{PrylutskaGrynyukGrebinyketal.2017, author = {Prylutska, Svitlana and Grynyuk, I. and Grebinyk, Anna and Hurmach, V. and Shatrava, Iu. and Sliva, T. and Amirkhanov, V. and Prylutskyy, Yuriy and Matyshevska, Olga and Slobodyanik, M. and Frohme, Marcus and Ritter, Uwe}, title = {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}, series = {Nanoscale Research Letters}, volume = {12}, journal = {Nanoscale Research Letters}, number = {124}, issn = {1556-276X}, doi = {10.1186/s11671-017-1893-3}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-9273}, year = {2017}, abstract = {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.}, language = {en} } @article{GrebinykYashchukBashmakovaetal.2019, author = {Grebinyk, Anna and Yashchuk, Valeriy and Bashmakova, Nataliya and Gryn, Dmytro and Hagemann, Tobias and Naumenko, Antonina and Kutsevol, Nataliya and Dandekar, Thomas and Frohme, Marcus}, title = {A New Triple System DNA-Nanosilver-Berberine for Cancer Therapy}, series = {Applied Nanoscience}, journal = {Applied Nanoscience}, issn = {2190-5517}, doi = {10.1007/s13204-018-0688-x}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-10628}, year = {2019}, abstract = {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.}, language = {en} } @article{GrebinykPrylutskaGrynyuketal.2018, author = {Grebinyk, Anna and Prylutska, Svitlana and Grynyuk, I. and Kolp, Benjamin and Hurmach, V. and Sliva, T. and Amirkhanov, V. and Trush, V. and Matyshevska, Olga and Slobodyanik, M. and Prylutskyy, Yuriy and Frohme, Marcus and Ritter, Uwe}, title = {C60 Fullerene Effects on Diphenyl-N-(trichloroacetyl)-amidophosphate Interaction with DNA In Silico and Its Cytotoxic Activity Against Human Leukemic Cell Line In Vitro}, series = {Nanoscale Research Letters}, volume = {2018}, journal = {Nanoscale Research Letters}, issn = {1556-276X}, doi = {10.1186/s11671-018-2490-9}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-10515}, pages = {1 -- 9}, year = {2018}, abstract = {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.}, language = {en} }