Publikationen am Institut für Chemie und Biotechnik

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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.



https://doi.org/10.3390/ijms25053069
Nguyen, Thi-Huong; Chen, Li-Yu; Khan, Nida Zaman; Lindenbauer, Annerose; Bui, Van-Chien; Zipfel, Peter F.; Heinrich, Doris
The binding of the SARS-CoV-2 spike protein to platelet factor 4: a proposed mechanism for the generation of pathogenic antibodies. - In: Biomolecules, ISSN 2218-273X, Bd. 14 (2024), 3, 245, S. 1-14

Pathogenic platelet factor 4 (PF4) antibodies contributed to the abnormal coagulation profiles in COVID-19 and vaccinated patients. However, the mechanism of what triggers the body to produce these antibodies has not yet been clarified. Similar patterns and many comparable features between the COVID-19 virus and heparin-induced thrombocytopenia (HIT) have been reported. Previously, we identified a new mechanism of autoimmunity in HIT in which PF4-antibodies self-clustered PF4 and exposed binding epitopes for other pathogenic PF4/eparin antibodies. Here, we first proved that the SARS-CoV-2 spike protein (SP) also binds to PF4. The binding was evidenced by the increase in mass and optical intensity as observed through quartz crystal microbalance and immunosorbent assay, while the switching of the surface zeta potential caused by protein interactions and binding affinity of PF4-SP were evaluated by dynamic light scattering and isothermal spectral shift analysis. Based on our results, we proposed a mechanism for the generation of PF4 antibodies in COVID-19 patients. We further validated the changes in zeta potential and interaction affinity between PF4 and SP and found that their binding mechanism differs from ACE2-SP binding. Importantly, the PF4/SP complexes facilitate the binding of anti-PF4/Heparin antibodies. Our findings offer a fresh perspective on PF4 engagement with the SARS-CoV-2 SP, illuminating the role of PF4/SP complexes in severe thrombotic events.



https://doi.org/10.3390/biom14030245
Köhler, Michael; Ehrhardt, Linda; Günther, Mike; Böhme, Manfred; Cao-Riehmer, Jialan
Low abundant bacteria reflect soil specificity - analysis of bacterial communities from archaeological investigation of pre-industrial saline ash deposits of Bad Dürrenberg (Germany). - In: Environments, ISSN 2076-3298, Bd. 11 (2024), 3, 42, S. 1-20

Six soil samples from three layers of an archaeological investigation profile from a pre-industrial ash deposit place have been investigated by NGS analyses of 16 S rRNA. The three pairs of sample originate from top soil (internal reference), from an intermediate ash layer and from a lower ash layer, formed about two centuries ago. In addition to general abundant bacteria, special genera known as halophilic or alkaline-tolerant have been found as expected from the history of the place and from the measured pH-value and conductivity measurements. The close relations between samples of pairs and the differences between the three soil layers are clearly indicated by abundance correlation and PCA-diagrams. Comparative PCA correlation plots including samples from an archaeological excavation site dedicated to pre-industrial coal mining illustrate the high distinguishability of investigated soils. These relations are particular clearly shown when lower abundant bacteria are regarded. The investigations are a further example for the “ecological memory of soil” reflecting the strong human impact on this pre-industrial embossed place.



https://doi.org/10.3390/environments11030042
Küstner, Merle Johanna; Eckstein, Diana; Brauer, Dana; Mai, Patrick; Hampl, Jörg; Weise, Frank; Schuhmann, Berit; Hause, Gerd; Glahn, Felix; Foth, Heidi; Schober, Andreas
Modular air-liquid interface aerosol exposure system (MALIES) to study toxicity of nanoparticle aerosols in 3D-cultured A549 cells in vitro. - In: Archives of toxicology, ISSN 1432-0738, Bd. 98 (2024), 4, S. 1061-1080

We present a novel lung aerosol exposure system named MALIES (modular air-liquid interface exposure system), which allows three-dimensional cultivation of lung epithelial cells in alveolar-like scaffolds (MatriGrids®) and exposure to nanoparticle aerosols. MALIES consists of multiple modular units for aerosol generation, and can be rapidly assembled and commissioned. The MALIES system was proven for its ability to reliably produce a dose-dependent toxicity in A549 cells using CuSO4 aerosol. Cytotoxic effects of BaSO4- and TiO2-nanoparticles were investigated using MALIES with the human lung tumor cell line A549 cultured at the air-liquid interface. Experiments with concentrations of up to 5.93 × 10^5 (BaSO4) and 1.49 × 10^6 (TiO2) particles/cm^3, resulting in deposited masses of up to 26.6 and 74.0 µg/cm^2 were performed using two identical aerosol exposure systems in two different laboratories. LDH, resazurin reduction and total glutathione were measured. A549 cells grown on MatriGrids® form a ZO-1- and E-Cadherin-positive epithelial barrier and produce mucin and surfactant protein. BaSO4-NP in a deposited mass of up to 26.6 µg/cm^2 resulted in mild, reversible damage (˜ 10% decrease in viability) to lung epithelium 24 h after exposure. TiO2-NP in a deposited mass of up to 74.0 µg/cm^2 did not induce any cytotoxicity in A549 cells 24 h and 72 h after exposure, with the exception of a 1.7 fold increase in the low exposure group in laboratory 1. These results are consistent with previous studies showing no significant damage to lung epithelium by short-term treatment with low concentrations of nanoscale BaSO4 and TiO2 in in vitro experiments.



https://doi.org/10.1007/s00204-023-03673-3
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.



https://doi.org/10.1016/j.jddst.2023.105275
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.



https://doi.org/10.1016/B978-0-323-85595-2.00005-0
Jaster, Jonas; Dreßler, Elias; Geitner, Robert; Groß, Gregor Alexander
Synthesis and spectroscopic characterization of furan-2-carbaldehyde-d. - In: Molbank, ISSN 1422-8599, Bd. 2023 (2023), 2, M1654, S. 1-9

Here, we present a protocol for the one-step synthesis of the title compound in quantitative yield using adapted Vilsmeier conditions. The product was characterized by 1H-,2H-,13C-NMR-, as well as IR and Raman spectroscopy. Spectral data are given in detail.



https://doi.org/10.3390/M1654
Eckstein, Daniel; Schumann, Berit; Glahn, Felix; Krings, Oliver; Schober, Andreas; Foth, Heidi
Comparison of a 3D co-culture and a mini organ culture by testing barium sulphate and titanium dioxide nanoparticle aerosols. - In: Naunyn-Schmiedeberg's archives of pharmacology, ISSN 1432-1912, Bd. 396 (2023), 1, P055, S. S37

https://doi.org/10.1007/s00210-023-02397-6
Bui, Van-Chien; Nguyen, Thi-Huong
Mechanics of leukemic T-cell. - In: Journal of molecular recognition, ISSN 1099-1352, Bd. 36 (2023), 7, e3019, S. 1-7

Cell mechanics is a factor that determines cell growth, migration, proliferation, or differentiation, as well as trafficking inside the cytoplasm and organization of organelles. Knowledge about cell mechanics is critical to gaining insight into these biological processes. Here, we used atomic force microscopy to examine the elasticity, an important parameter of cell mechanics, of non-adherent Jurkat leukemic T-cells in both interphase and mitotic phases. We found that the elasticity of an individual cell does not significantly change at interphase. When a cell starts to divide, its elasticity increases in the transition from metaphase to telophase during normal division while the cell is stiffened right after it enters mitosis during abnormal division. At the end of the division, the cell elasticity gradually returned to the value of the mother cell. These changes may originate from the changes in cell surface tension during modulating actomyosin at the cleavage furrow, redistributing cell organelles, and constricting the contractile ring to sever mother cell to form daughters. The difference in elasticity patterns suggests that there is a discrepancy in the redistribution of the cell organelles during normal and abnormal division.



https://doi.org/10.1002/jmr.3019
Nguyen, Thi-Huong; Wang, Hanqing; Chen, Li-Yu; Echtermeyer, Danny; Pliquett, Uwe
Modulating SARS-CoV-2 spike protein reactivity through moderate electric fields: a pathway to innovative therapies. - In: ACS omega, ISSN 2470-1343, Bd. 8 (2023), 48, S. 45952-45960

In the quest for effective COVID-19 treatments and vaccines, traditional biochemical methods have been paramount, yet the challenge of accommodating diverse viral mutants persists. Recent simulations propose an innovative physical strategy involving an external electric field applied to the SARS-CoV-2 spike protein, demonstrating a reduced viral binding potential. However, limited empirical knowledge exists regarding the characteristics of the spike protein after E-field treatment. Our study addresses this gap by employing diverse analytical techniques to elucidate the impact of low/moderate E-field intensity on the binding of the SARS-CoV-2 spike protein to the ACE2 receptor. Through comprehensive analysis, we unveil a substantial reduction in the spike protein binding capacity validated via enzyme-linked immunosorbent assay and quartz crystal microbalance experiments. Remarkably, the E-field exposure induces significant protein structure rearrangement, leading to an enhanced negative surface zeta potential confirmed by dynamic light scattering. Circular dichroism spectroscopy corroborates these structural changes, showing alterations in the secondary protein structures. This study provides insights into SARS-CoV-2 spike protein modification under an E-field pulse, potentially paving the way for nonbiochemical strategies to mitigate viral reactivity and opening avenues for innovative therapeutic and preventive approaches against COVID-19 and its evolving variants.



https://doi.org/10.1021/acsomega.3c06811