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Prylutska, Svitlana; Grebinyk, Anna; Ponomarenko, Stanislav; Gövem, Defne; Chumachenko, Vasyl; Kutsevol, Nataliya; Petrovsky, Mykola; Ritter, Uwe; Frohme, Marcus; Piosik, Jacek; Prylutskyy, Yuriy
Toxicity of water-soluble D-g-PNIPAM polymers in a complex with chemotherapy drugs and mechanism of their action in vitro. - In: International journal of molecular sciences, ISSN 1422-0067, Bd. 25 (2024), 5, 3069, S. 1-15

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.
Horak, Iryna; Skaterna, Tetiana; Lugovskyi, Serhii; Krysiuk, Iryna; Tykhomyrov, Artem; Prylutska, Svitlana; Tverdokhleb, Nina; Senenko, Anton; Cherepanov, Vsevolod; Drobot, Liudmyla; Matyshevska, Olga; Ritter, Uwe; Prylutskyy, Yuriy
Antimetastatic lung cancer therapy using alkaloid Piperlongumine noncovalently bound to С60 fullerene. - In: Journal of drug delivery science and technology, Bd. 92 (2024), 105275, S. 1-10

A novel nanoformulation, C60 fullerene loaded with a plant alkaloid Piperlongumine (PL) molecules (C60-PL nanocomplex), as a potential drug for the treatment of highly metastatic lung cancer was created and characterized by using ultrasonic technology, computer simulation, atomic force and scanning tunneling microscopy. The aim of the study was to evaluate the antimetastatic potential of PL alone and the C60-PL nanocomplex using Lewis lung carcinoma (LLC) cell line as a model. Evidence has been obtained that the 2:1C60-PL nanocomplex is a potent agent capable of effectively reducing the survival, migration and invasion of LLC cells in vitro, as well as tumor growth and metastasis in vivo compared to free PL. These effects in cell behavior were shown to be associated with an increased Bax expression and high level of cleaved PARP confirming the proapototic potential of C60-PL nanocomplex as well as down-regulation of the mRNA of epithelial-mesenchymal transition regulator Twist1 and cancer stem cell marker CD44, a reduced level of phosphorylated mTOR and adaptor protein Ruk/CIN85. Histological analysis of the lung tissue of LLC-bearing mice showed that in animals that received the C60-PL nanocomplex, the regression of metastases prevailed over their growth. The obtained results allow to conclude that the proposed C60-PL nanocomplex represents a promising drug for the treatment of metastatic lung cancer.
Grebinyk, Anna; Prylutska, Svitlana; Grebinyk, Sergii; Prylutskyy, Yuriy; Ritter, Uwe; Matyshevska, Olga; Dandekar, Thomas; Frohme, Marcus
Toward photodynamic cancer chemotherapy with C60-Doxorubicin nanocomplexes. - In: Nanomaterials for photodynamics therapy, (2023), S. 489-522

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. The dual functionality of C60 as a photosensitizer and a drug nanocarrier sets an opportunity to improve the efficiency of chemotherapeutic drugs for cancer cells. Pristine C60 demonstrates time-dependent accumulation with predominant mitochondrial localization in cancer cells. Nanomolar amounts of C60-drug nanocomplexes in 1:1 and 2:1 molar ratios improve the efficiency of cell treatment, complementing it with photodynamic approach. The cooperative enhancement interactions between mechanisms of chemo- and photodynamic therapies contribute to the obtained synergistic effect (namely “1+1>2”). A strong synergy of treatments arising from the combination of C60-mediated drug delivery and C60 photoexcitation indicates that a combination of chemo- and photodynamic treatments with C60-drug nanoformulations could provide a promising synergetic approach for cancer treatment.
Radivoievych, Aleksandar; Prylutska, Svitlana; Zolk, Oliver; Ritter, Uwe; Frohme, Marcus; Grebinyk, Anna
Comparison of sonodynamic treatment set-ups for cancer cells with organic sonosensitizers and nanosonosensitizers. - In: Pharmaceutics, ISSN 1999-4923, Bd. 15 (2023), 11, 2616, S. 1-21

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.
Motuziuk, Olexandr; Nozdrenko, Dmytro; Prylutska, Svitlana; Bogutska, Kateryna; Mishchenko, Iryna; Abramchuk, Olga; Khrapatyi, Sergii; Ritter, Uwe; Prylutskyy, Yuriy
C60 fullerene reduces the level of fluctuations in the force response of muscle gastrocnemius in chronically alcoholized rats. - In: Applied nanoscience, ISSN 2190-5517, Bd. 13 (2023), 10, S. 7057-7067

The biomechanical parameters of muscle gastrocnemius contraction and biochemical parameters of blood and muscle tissue in rats after chronic alcoholization for 3, 6, and 9 months were studied. The oral administration of C60 fullerene aqueous solution (C60FAS) at doses of 0.5, 1, and 2 mg/kg throughout the experiment was used as a therapeutic agent. C60FAS in each of the experimental groups was administered in three ways: 1 h before alcohol intake, together with alcohol, and 1 h after alcohol intake. The most significant positive effects were recorded when alcohol and C60FAS were administered together at the optimal dose of 1 mg/kg. So, the increase in muscle gastrocnemius contraction force was 20 ± 1%, 33 ± 2% and 65 ± 3% (p < 0.05) compared with control at 3, 6, and 9 months alcoholization, respectively, as well as a high level of its fluctuations correction was observed throughout the experiment. Biochemical parameters such as blood levels of creatinine, creatine phosphokinase, lactate and lactate dehydrogenase as well as pro- and antioxidant balance (content of hydrogen peroxide and reduced glutathione, as well as catalase, selenium-dependent glutathione peroxidase and superoxide dismutase activities) in muscle gastrocnemius tissues decreased from 15 ± 2% (3 months of alcoholization) to 45 ± 2% (9 months of alcoholization) (p < 0.05) compared to controls. The results indicate promising prospects for the use of water-soluble C60 fullerenes, as powerful antioxidants, for the correction of pathological conditions of the muscular system arising from alcohol intoxication.
Motuziuk, Olexandr; Nozdrenko, Dmytro; Prylutska, Svitlana; Vareniuk, Igor; Bogutska, Kateryna; Braniuk, Serhii; Korotkyi, Olexandr; Prylutskyy, Yuriy; Ritter, Uwe; Piosik, Jacek
The effect of C60 fullerene on the mechanokinetics of muscle gastrocnemius contraction in chronically alcoholized rats. - In: Heliyon, ISSN 2405-8440, Bd. 9 (2023), 8, e18745, S. 1-10

The C60 fullerene effect (oral administration at a dose of 1 mg kg−1) on the selected biomechanical parameters of muscle gastrocnemius contraction, biochemical indicators of blood and muscle tissue as well as histological changes in rat muscle tissue after chronic alcoholization for 3, 6 and 9 months was studied in detail. Water-soluble C60 fullerenes were shown to reduce the pathological processes development in the muscle apparatus by an average of (35-40)%. In particular, they reduced the time occurrence of fatigue processes in muscle during the long-term development of alcoholic myopathy and inhibited oxidative processes in muscle, thereby preventing its degradation. These findings open up the possibility of using C60 fullerenes as potent antioxidants for the correction of the pathological conditions of the muscle system arising from alcohol intoxication.
Zavodovskiy, Danylo O.; Bulgakova, Nataliya V.; Sokolowska, Inna; Prylutskyy, Yuriy I.; Ritter, Uwe; Gonchar, Olga O.; Kostyukov, Alexander I.; Vlasenko, Oleh V.; Butowska, Kamila; Borowik, Agnieszka; Piosik, Jacek; Maznychenko, Andriy
Water-soluble pristine C60 fullerenes attenuate isometric muscle force reduction in a rat acute inflammatory pain model. - In: BMC musculoskeletal disorders, ISSN 1471-2474, Bd. 24 (2023), 606, S. 1-8

Background: Being a scavenger of free radicals, C60 fullerenes can influence on the physiological processes in skeletal muscles, however, the effect of such carbon nanoparticles on muscle contractility under acute muscle inflammation remains unclear. Thus, the aim of the study was to reveal the effect of the C60 fullerene aqueous solution (C60FAS) on the muscle contractile properties under acute inflammatory pain. Methods: To induce inflammation a 2.5% formalin solution was injected into the rat triceps surae (TS) muscle. High-frequency electrical stimulation has been used to induce tetanic muscle contraction. A linear motor under servo-control with embedded semi-conductor strain gauge resistors was used to measure the muscle tension. Results: In response to formalin administration, the strength of TS muscle contractions in untreated animals was recorded at 23% of control values, whereas the muscle tension in the C60FAS-treated rats reached 48%. Thus, the treated muscle could generate 2-fold more muscle strength than the muscle in untreated rats. Conclusions: The attenuation of muscle contraction force reduction caused by preliminary injection of C60FAS is presumably associated with a decrease in the concentration of free radicals in the inflamed muscle tissue, which leads to a decrease in the intensity of nociceptive information transmission from the inflamed muscle to the CNS and thereby promotes the improvement of the functional state of the skeletal muscle.
Finkelmeyer, Sarah; Askins, Erik J.; Eichhorn, Jonas; Ghosh, Soumik; Siegmund, Carmen; Täuscher, Eric; Dellith, Andrea; Hupfer, Maximilian; Dellith, Jan; Ritter, Uwe; Strzalka, Joseph; Glusac, Ksenija; Schacher, Felix; Presselt, Martin
Tailoring the weight of surface and intralayer edge states to control LUMO energies. - In: Advanced materials, ISSN 1521-4095, Bd. 35 (2023), 40, 2305006, S. 1-11

The energies of the frontier molecular orbitals determine the optoelectronic properties in organic films, which are crucial for their application, and strongly depend on the morphology and supramolecular structure. The impact of the latter two properties on the electronic energy levels relies primarily on nearest-neighbor interactions, which are difficult to study due to their nanoscale nature and heterogeneity. Here, an automated method is presented for fabricating thin films with a tailored ratio of surface to bulk sites and a controlled extension of domain edges, both of which are used to control nearest-neighbor interactions. This method uses a Langmuir–Schaefer-type rolling transfer of Langmuir layers (rtLL) to minimize flow during the deposition of rigid Langmuir layers composed of π-conjugated molecules. Using UV–vis absorption spectroscopy, atomic force microscopy, and transmission electron microscopy, it is shown that the rtLL method advances the deposition of multi-Langmuir layers and enables the production of films with defined morphology. The variation in nearest-neighbor interactions is thus achieved and the resulting systematically tuned lowest unoccupied molecular orbital (LUMO) energies (determined via square-wave voltammetry) enable the establishment of a model that functionally relates the LUMO energies to a morphological descriptor, allowing for the prediction of the range of accessible LUMO energies.
Täuscher, Eric; Freiberger, Emma
Cholesterin aus Hirn. - In: Nachrichten aus der Chemie, ISSN 1439-9598, Bd. 71 (2023), 1, S. 30-32

Cholesterin hat es bis in den Alltagssprachgebrauch gebracht. Allein deshalb ist es für Praktika im Chemiestudium ein interessanter Vertreter der Steroide. Zudem ist es einfach zu gewinnen.

Täuscher, Eric; Freiberger, Emma
Cholesterin aus Hirn. - In: Nachrichten aus der Chemie, ISSN 1868-0054, Bd. 71 (2023), 1, S. 30-32

Cholesterin hat es bis in den Alltagssprachgebrauch gebracht. Allein deshalb ist es für Praktika im Chemiestudium ein interessanter Vertreter der Steroide. Zudem ist es einfach zu gewinnen.