Purpose: The present study deals with the in vitro evaluation of the potential use of coordination compound-based zinc oxide (ZnO) nanoparticles (NPs) for the treatment of triple negative breast cancer cells (TNBrCa). As BrCa is one of the most prevalent cancer types and TNBrCa treatment is difficult due to poor prognosis and a high metastasis rate, finding a more reliable treatment option should be of the utmost interest. Methods: Prepared by reacting zinc carboxylates (formate, acetate, propionate, butyrate, isobutyrate, valerate) and hexamethylenetetramine, 4 distinct coordination compounds were further subjected to two modes of conversion into ZnO NPs - ultrasonication with oleic acid or heating of pure precursors in an air atmosphere. After detailed characterization, the resulting ZnO NPs were subjected to in vitro testing of cytotoxicity toward TNBrCa and normal breast epithelial cells. Further, their biocompatibility was evaluated. Results: The resulting ZnO NPs provide distinct morphological features, size, biocompatibility, and selective cytotoxicity toward TNBrCa cells. They internalize into two types of TNBrCa cells and imbalance their redox homeostasis, influencing their metabolism, morphology, and ultimately leading to their death via apoptosis or necrosis. Conclusion: The crucial properties of ZnO NPs seem to be their morphology, size, and zinc content. The ZnO NPs with the most preferential values of all three properties show great promise for a future potential use in the therapy of TNBrCa.
- MeSH
- antitumorózní látky chemie farmakologie MeSH
- apoptóza účinky léků MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nanočástice chemie MeSH
- oxid zinečnatý chemie farmakologie MeSH
- proliferace buněk účinky léků MeSH
- triple-negativní karcinom prsu patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Coronavirus disease (COVID-19) caused by SARS-CoV-2 has spread since the end of 2019 and has resulted in a pandemic with unprecedented socioeconomic consequences. This situation has created enormous demand for the improvement of current diagnostic methods and the development of new diagnostic methods for fast, low-cost and user-friendly confirmation of SARS-CoV-2 infection. This critical review focuses on viral electrochemical biosensors that are promising for the development of rapid medical COVID-19 diagnostic tools. The molecular biological properties of SARS-CoV-2 as well as currently known biochemical attributes of infection necessary for biosensor development are outlined. The advantages and drawbacks of conventional diagnostic methods, such as quantitative reverse-transcription polymerase chain reaction (qRT-PCR), are critically discussed. Electrochemical biosensors focusing on viral nucleic acid and whole viral particle detection are highlighted and discussed in detail. Finally, future perspectives on viral electrochemical biosensor development are briefly mentioned.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Recent progress in nanomedicine and targeted therapy brings new breeze into the field of therapeutic applications of tyrosine kinase inhibitors (TKIs). These drugs are known for many side effects due to non-targeted mechanism of action that negatively impact quality of patients' lives or that are responsible for failure of the drugs in clinical trials. Some nanocarrier properties provide improvement of drug efficacy, reduce the incidence of adverse events, enhance drug bioavailability, helps to overcome the blood-brain barrier, increase drug stability or allow for specific delivery of TKIs to the diseased cells. Moreover, nanotechnology can bring new perspectives into combination therapy, which can be highly efficient in connection with TKIs. Lastly, nanotechnology in combination with TKIs can be utilized in the field of theranostics, i.e. for simultaneous therapeutic and diagnostic purposes. The review provides a comprehensive overview of advantages and future prospects of conjunction of nanotransporters with TKIs as a highly promising approach to anticancer therapy.
- MeSH
- inhibitory proteinkinas aplikace a dávkování chemie farmakologie MeSH
- lidé MeSH
- nádory farmakoterapie MeSH
- nanomedicína * MeSH
- nanostruktury aplikace a dávkování chemie MeSH
- systémy cílené aplikace léků * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Publikační typ
- abstrakt z konference MeSH
Dietary supplementation with polyunsaturated fatty acids (PUFA) n-3 can affect cutaneous wound healing; however, recent findings demonstrate the variable extent of their influence on the quality of healing. Here, we compare the effect of several dietary oils, containing different levels of PUFA n-3 and PUFA n-6, on wound healing in the rat model. Rats were fed the feed mixture with 8% palm oil (P), safflower oil (S), fish oil (F) or Schizochytrium microalga extract (Sch) and compared to the animals fed by control feed mixture (C). Dorsal full-thickness cutaneous excisions were performed after 52 days of feeding and skin was left to heal for an additional 12 days. Histopathological analysis of skin wounds was performed, including immune cells immunolabeling and the determination of hydroxyproline amount as well as gene expression analyses of molecules contributing to different steps of the healing. Matrix-assisted-laser-desorption-ionization mass-spectrometry-imaging (MALDI-MSI) was used to determine the amount of collagen α-1(III) chain fragment in healing samples. Treatment by Schizochytrium extract resulted in decrease in the total wound area, in contrast to the safflower oil group where the size of the wound was larger when comparing to control animals. Diet with Schizochytrium extract and safflower oils displayed a tendency to increase the number of new vessels. The number of MPO-positive cells was diminished following any of oil treatment in comparison to the control, but their highest amount was found in animals with a fish oil diet. On the other hand, the number of CD68-positive macrophages was increased, with the most significant enhancement in the fish oil and safflower oil group. Hydroxyproline concentration was the highest in the safflower oil group but it was also enhanced in all other analyzed treatments in comparison to the control. MALDI-MSI signal intensity of a collagen III fragment decreased in the sequence C > S > Sch > P > F treatment. In conclusion, we observed differences in tissue response during healing between dietary oils, with the activation of inflammation observed following the treatment with oil containing high eicosapentaenoic acid (EPA) level (fish oil) and enhanced healing features were induced by the diet with high content of docosahexaenoic acid (DHA, Schizochytrium extract).
- MeSH
- antigeny CD8 metabolismus MeSH
- dietní tuky nenasycené aplikace a dávkování farmakologie MeSH
- hojení ran účinky léků MeSH
- indoly chemie MeSH
- kolagen typ III metabolismus MeSH
- krysa rodu rattus MeSH
- kůže účinky léků zranění metabolismus MeSH
- kyseliny mastné omega-3 analýza MeSH
- kyseliny mastné omega-6 analýza MeSH
- makrofágy imunologie MeSH
- modely nemocí na zvířatech MeSH
- palmový olej aplikace a dávkování chemie farmakologie MeSH
- rybí oleje aplikace a dávkování chemie farmakologie MeSH
- spektrometrie hmotnostní - ionizace laserem za účasti matrice MeSH
- světlicový olej aplikace a dávkování chemie farmakologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
Metal-based coordination compounds, including the well-known cytostatic drug cisplatin, are widely used in the anticancer therapy. Generally, they exhibit high cytotoxicity not only towards malignant cells, but also towards non-malignant cells, which represents main problem of their clinical use. Herein, we describe the synthesis, characterization and biological testing of three trinuclear nickel(II) coordination compounds. Central nickel atoms are bridged by trithiocyanurate anion and coordinated by triamine and bis-benzimidazoles, respectively. To delineate a potential usage in anticancer therapy, we encapsulated the most cytotoxic complex into biomacromolecular protein cage apoferritin (FRT), forming FRTNi. FRT encapsulation markedly decreased the hemotoxicity of free Ni compounds. Despite FRTNi can be internalized through passive targeting by enhanced permeability and retention effect, we further introduced active targeting utilizing folate receptor (FR) via folic acid (FA)-modified FRT (FRTNiFA). Using breast cancer cell lines T-47D (FR+), MCF-7 (FR-) and non-malignant mammary gland derived cell line HBL-100 (FR-), we show pronounced FR-dependent internalization of FRTNiFA. Overall, we demonstrate that the FRT macromolecular nanocarrier provides a very low off-target toxicity, which could enable the use of highly toxic Ni compounds in cancer nanomedicine.
- MeSH
- apoptóza účinky léků MeSH
- biokompatibilní materiály farmakologie MeSH
- buněčná smrt účinky léků MeSH
- buněčné klony MeSH
- endocytóza účinky léků MeSH
- ferritin metabolismus MeSH
- komplexní sloučeniny chemická syntéza chemie farmakologie MeSH
- kyselina listová farmakologie MeSH
- lidé MeSH
- ligandy MeSH
- nádorové buněčné linie MeSH
- nikl farmakologie MeSH
- pohyb buněk účinky léků MeSH
- proliferace buněk účinky léků MeSH
- proteiny vázající železo metabolismus MeSH
- receptory buněčného povrchu metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
In the present study, two binuclear copper(II) coordination compounds bridged by hydroxy- and thiodipropionic acid have been synthesized. The structure of compounds was determined by X-ray crystallography. The central copper atoms exist in square pyramidal surroundings. Basal plane is formed by nitrogen atoms of amines and oxygen atoms of bridges, whereas apical positions are occupied by oxygen atoms of coordinated water molecules. Temperature dependence study of magnetic susceptibility proved strong antiferromagnetic exchange between copper atoms in hydroxy-bridged complex. These coordination compounds were also tested for their biological activities in vitro. Both coordination compounds exhibit pronounced cytocompatibility in mammalian epithelial cells with no induction of oxidative stress and DNA fragmentation. Moreover, synthesized compounds are hemocompatible and do not alter expression of a marker of multiple cellular stress, p53. On the other hand, both compounds had stimulatory effect on expression of metallothioneins (MT-1/2 and MT-3). Antimicrobial testing on Escherichia coli, Staphylococcus aureus and methicillin-resistant Staphylococcus aureus revealed that both copper compounds exhibit antibacterial activity regardless the cell wall composition. Overall, current work presents a synthesis of Cu(II) coordination compounds with interesting biological behavior and with a promising potential to be further tested in pre-clinical models.
- MeSH
- antibakteriální látky chemická syntéza chemie farmakologie MeSH
- biokompatibilní materiály MeSH
- hemolýza účinky léků MeSH
- hojení ran účinky léků MeSH
- komplexní sloučeniny chemická syntéza chemie MeSH
- lidé MeSH
- měď chemie MeSH
- methicilin rezistentní Staphylococcus aureus účinky léků MeSH
- mikrobiální testy citlivosti MeSH
- molekulární struktura MeSH
- nádorové buněčné linie MeSH
- propionáty chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
Nanoparticular form of titanium dioxide (TiO2 NPs) belongs to important industrial material. Despite being widely used, serious contradictions regarding biosafety of TiO2 NPs remain. We anticipate that such discrepancies could be due to a lack of understanding of a linkage between TiO2 NPs phase composition and cytotoxicity. Therefore, we synthesized two types of biphasic TiO2 NPs differing in an anatase-brookite phase composition. The study presents an array of in vitro data suggesting that TiO2 NPs with a prevailing anatase phase composition possess higher cytotoxicity compared to TiO2 NPs with an equal anatase-brookite crystallinity. This phenomenon was evidenced by significantly higher inhibition of metabolic activity and growth of epithelial and neuroblast-like cells. Moreover, anatase-prevailing TiO2 NPs tend to produce higher amount of reactive oxygen species resulting in DNA fragmentation. Further insights into the molecular aspects of cytotoxicity of anatase-prevailing TiO2 NPs were obtained by comparative proteomics delineating that TiO2 NPs deregulate expression of a variety of proteins and associated pathways. This inevitably results in a decreased cellular ability to detoxify reactive oxygen species and respond to various stress conditions. The study provides novel data that add another piece to the jigsaw of the relation between structural features of NPs and biosafety.
- MeSH
- buněčné linie MeSH
- epitelové buňky účinky léků metabolismus MeSH
- kovové nanočástice chemie toxicita ultrastruktura MeSH
- krystalografie rentgenová MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- oxidační stres * MeSH
- reaktivní formy kyslíku metabolismus MeSH
- titan chemie toxicita MeSH
- transmisní elektronová mikroskopie MeSH
- viabilita buněk účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
