@article{RadivoievychSchnepelPrylutskaetal.2024, author = {Radivoievych, Aleksandar and Schnepel, Sophia and Prylutska, Svitlana and Ritter, Uwe and Zolk, Oliver and Frohme, Marcus and Grebinyk, Anna}, title = {From 2D to 3D In Vitro World: Sonodynamically-Induced Prooxidant Proapoptotic Effects of C60-Berberine Nanocomplex on Cancer Cells}, series = {Cancers}, volume = {16}, journal = {Cancers}, number = {18}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-19438}, year = {2024}, abstract = {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.}, 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} } @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{PrylutskaGrynyukGrebinyketal.2017, author = {Prylutska, Svitlana and Grynyuk, I. and Grebinyk, Anna and Hurmach, V. and Shatrava, Iu. and Sliva, T. and Amirkhanov, Volodymyr 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}, 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{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{LiAmirkhanyanGrebinyketal.2025, author = {Li, Xiangkun and Amirkhanyan, Zohrab and Grebinyk, Anna and Gross, Matthias and Komar, Yuliia and Riemer, Felix and Asoyan, Aida and Boonpornprasert, Prach and Borchert, Paul and Davtyan, Hakob and Dmytriiev, Dmytro and Frohme, Marcus and Hoffmann, Andreas and Krasilnikov, Mikhail and Loisch, Gregor and Lotfi, Zahra and M{\"u}ller, Frieder and Schmitz, Michael and Obier, Frank and Oppelt, Anne and Philipp, Sebastian and Richard, Christopher and Vashchenko, Grygorii and Villani, Daniel and Worm, Steven and Stephan, Frank}, title = {Demonstration of ultra-high dose rate electron irradiation at FLASHlab@PITZ}, series = {Physics in Medicine \& Biology}, volume = {70}, journal = {Physics in Medicine \& Biology}, number = {5}, publisher = {Institute of Physics Publishing (IOP)}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-20092}, year = {2025}, abstract = {Objective. The photo injector test facility at DESY in Zeuthen (PITZ) is building up an R\&D platform, known as FLASHlab@PITZ, for systematically studying the FLASH effect in cancer treatment with its high-brightness electron beams, which can provide a uniquely large dose parameter range for radiation experiments. In this paper, we demonstrate the capabilities by experiments with a reduced parameter range on a startup beamline and study the potential performance of the full beamline by simulations. Approach. To measure the dose, Gafchromic films are installed both in front of and after the samples; Monte Carlo simulations are conducted to predict the dose distribution during beam preparation and help understand the dose distribution inside the sample. Plasmid DNA is irradiated under various doses at conventional and ultra-high dose rate (UHDR) to study the DNA damage by radiations. Start-to-end simulations are performed to verify the performance of the full beamline. Main results. On the startup beamline, reproducible irradiation has been established with optimized electron beams and the delivered dose distributions have been measured with Gafchromic films and compared to FLUKA simulations. The functionality of this setup has been further demonstrated in biochemical experiments at conventional dose rate of 0.05 Gy s-1 and UHDR of several 105 Gy s-1 and a varying dose up to 60 Gy, with the UHDR experiments finished within a single RF pulse (less than 1 millisecond); the observed conformation yields of the irradiated plasmid DNA revealed its dose-dependent radiation damage. The upgrade to the full FLASHlab@PITZ beamline is justified by simulations with homogeneous radiation fields generated by both pencil beam scanning and scattering beams. Significance. With the demonstration of UHDR irradiation and the simulated performance of the new beamline, FLASHlab@PITZ will serve as a powerful platform for studying the FLASH effects in cancer treatment.}, language = {en} } @inproceedings{LiAmirkhanyanAftabetal.2024, author = {Li, Xiangkun and Amirkhanyan, Zohrab and Aftab, Namra and Boonpornprasert, Prach and Dmytriiev, Dmytro and Frohme, Marcus and Georgiev, Georgi and Grebinyk, Anna and Gross, Matthias and Hoffmann, Andreas and Komar, Yuliia and Krasilnikov, Mikhail and Loisch, Gregor and Oppelt, Anne and Richard, Christopher and Riemer, F. and Philipp, Sebastian and Schmitz, Michael and M{\"u}ller, Frieder and Obier, Frank and Vashchenko, Grygorii and Worm, Steven and Stephan, Frank}, 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} } @inproceedings{KrasilnikovAboulbanineAdhikarietal.2023, author = {Krasilnikov, Mikhail and Aboulbanine, Zakaria and Adhikari, Gowri and Aftab, Namra and Asoyan, Aida and Davtyan, Hakob and Georgiev, Georgi and Good, James and Grebinyk, Anna and Gross, Matthias and Hoffmann, Andreas and Kongmon, Ekkachai and Li, Xiangkun and Lueangaramwong, Anusorn and Melkumyan, David and Mohanty, Sandeep and Niemczyk, Raffael and Oppelt, Anne and Qian, Houjun and Richard, Christopher and Schneidmiller, Evgeny and Stephan, Frank and Vashchenko, Grygorii}, title = {THz SASE FEL at PITZ: lasing at a wavelength of 100μm}, series = {IPAC'23 : 14th International Particle Accelerator Conference, 7-12 May 2023, Venice, Italy : proceedings}, booktitle = {IPAC'23 : 14th International Particle Accelerator Conference, 7-12 May 2023, Venice, Italy : proceedings}, editor = {Istituto Nazionale Di Fisca Nucleare,}, publisher = {JACoW Publishing}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-21113}, pages = {3948 -- 3951}, year = {2023}, abstract = {Development of an accelerator-based tunable THz source prototype for pump-probe experiments at the European XFEL is ongoing at the Photo Injector Test facility at DESY in Zeuthen (PITZ). The proof-of-principle experiments on the THz SASE FEL are performed utilizing the LCLS-I undulator installed in the PITZ beamline. The first lasing at a center wavelength of 100 µm was observed in the summer of 2022. The lasing of the narrowband THz source was achieved using an electron beam with an energy of ~17 MeV and a bunch charge up to several nC. Optimization of beam transport and matching resulted in the measurement of THz radiation with a pulse energy of tens of µJ, measured with pyroelectric detectors. The THz FEL gain curves were measured by means of specially designed short coils along the undulator. The results of the first characterization of the THz source at PITZ will be presented.}, language = {en} } @inproceedings{GrossKuhlStephanetal.2023, author = {Gross, Matthias and Kuhl, Thorsten and Stephan, Frank and Li, Xiangkun and Philipp, Sebastian and Grebinyk, Anna and Khachatryan, Vitali and Qian, Houjun and Aboulbanine, Zakaria and Amirkhanyan, Zohrab and Riemer, Felix and Oppelt, Anne and Krasilnikov, Mikhail}, title = {A beam line setup for flash radiation therapy with focused electron beams at the Pitz facility at DESY in Zeuthen: basic concept and dosimetry simulations}, series = {IPAC'23 : 14th International Particle Accelerator Conference, 7-12 May 2023, Venice, Italy : proceedings}, booktitle = {IPAC'23 : 14th International Particle Accelerator Conference, 7-12 May 2023, Venice, Italy : proceedings}, editor = {Istituto Nazionale Di Fisca Nucleare,}, publisher = {JACoW Publishing}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-21132}, pages = {5000 -- 5003}, year = {2023}, abstract = {The aim of this work is to demonstrate the principal possibility to enhance the electron beam dose deposition in the depth of the sample for radiation therapy purposes. Trains of electron bunches of 22 MeV generated at PITZ are focused inside the sample using a dedicated fast deflector and a solenoid magnet. To explore the capabilities of the proposed setup, dose distributions are calculated for multiple electron bunches focused in a single point inside a water phantom. Electron beam focusing produces dose peaks with a tunable maximal dose depth which is interesting for healthy tissue sparing at the surface and enhancing treatment quality. The duration of the full bunch train is 1 ms. During this time interval, the FLASH effect could be efficiently triggered inside the irradiated target volume. Monte Carlo simulations based on the FLUKA code were performed to evaluate the depth dose curves distributions in a water phantom. Using the PITZ electron beam parameters, simulations have shown the possibility to produce a peak dose in water seven times higher than compared to the dose at the surface. Moreover, the RMS size homogeneous area around the maximal dose is approximately 25 mm.}, language = {en} } @inproceedings{GrossHoffmannGeorgievetal.2023, author = {Gross, Matthias and Hoffmann, Andreas and Georgiev, Georgi and Kuhl, Thorsten and Li, Xiangkun and Oppelt, Anne and Boonpornprasert, Prach and Philipp, Sebastian and Grebinyk, Anna and Vashchenko, Grygorii and Aftab, Namra and Adhikari, Gowri and Richard, Christopher and Stephan, Frank and Khachatryan, Vitali and Riemer, Felix and Krasilnikov, Mikhail and Amirkhanyan, Zohrab}, title = {Comparison of measurements and simulation results of dose for the FLASH radiation therapy beamline at PITZ}, series = {IPAC'23 : 14th International Particle Accelerator Conference, 7-12 May 2023, Venice, Italy : proceedings}, booktitle = {IPAC'23 : 14th International Particle Accelerator Conference, 7-12 May 2023, Venice, Italy : proceedings}, editor = {Istituto Nazionale Di Fisca Nucleare,}, publisher = {JACoW Publishing}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-21126}, pages = {4996 -- 4999}, year = {2023}, abstract = {The high-brightness electron beam at the Photo Injector Test facility at DESY in Zeuthen (PITZ) is now also used for FLASHlab@PITZ: an R\&D platform for studying radiation biology and the FLASH effect in radiation therapy. The available parameter space of the electron beam with a momentum of 22 MeV/c allows bunch charges from 10 pC up to 5nC, bunch durations of 0.1-60ps, and bunch train lengths up to 1 ms. The number of bunches in the single train can currently be varied between 1 and 1000 bunches, with an upgrade to 4500 foreseen in 2023. Radiation biology studies require accurate dose prediction, therefore Monte Carlo simulations based on the FLUKA code were performed. According to estimations, dose delivery of 0.002 Gy (low charge case 0.1pC) and 10Gy (high charge case 5nC) is possible, if the beam is confined to a circular area with a radius of 5 mm with a lead collimator. For the Monte Carlo simulations, the experimental setup was accurately modeled, including the exit window, lead collimator, etc. Dose measurements were used to compare simulations with experiments. Dose profiles were experimentally measured with Gafchromic films and then compared with Monte Carlo simulations. The first experiments at FLASHlab@PITZ in 2023 have demonstrated flexible dose options for studying the FLASH effect and radiation biology studies.}, language = {en} }