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Application of Advanced Microscopic Methods to Study the Interaction of Carboxylated Fluorescent Nanodiamonds with Membrane Structures in THP-1 Cells: Activation of Inflammasome NLRP3 as the Result of Lysosome Destabilization

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    SYSNO ASEP0509040
    Document TypeJ - Journal Article
    R&D Document TypeJournal Article
    Subsidiary JČlánek ve WOS
    TitleApplication of Advanced Microscopic Methods to Study the Interaction of Carboxylated Fluorescent Nanodiamonds with Membrane Structures in THP-1 Cells: Activation of Inflammasome NLRP3 as the Result of Lysosome Destabilization
    Author(s) Knötigová, P.T. (CZ)
    Mašek, J. (CZ)
    Hubatka, F. (CZ)
    Kotouček, J. (CZ)
    Kulich, P. (CZ)
    Šimečková, P. (CZ)
    Bartheldyová, E. (CZ)
    Machala, M. (CZ)
    Švadláková, T. (CZ)
    Krejsek, J. (CZ)
    Vaškovicová, Naděžda (UPT-D) RID, ORCID, SAI
    Skoupý, Radim (UPT-D) RID, ORCID, SAI
    Krzyžánek, Vladislav (UPT-D) RID, ORCID, SAI
    Macaulay, V. (GB)
    Katzuba, M. (GB)
    Fekete, Ladislav (FZU-D) RID, ORCID
    Ashcheulov, Petr (FZU-D) ORCID, RID
    Raška, M. (CZ)
    Kratochvílová, Irena (FZU-D) RID, ORCID, SAI
    Turánek, J. (CZ)
    Number of authors20
    Source TitleMolecular Pharmaceutics. - : American Chemical Society - ISSN 1543-8384
    Roč. 16, č. 8 (2019), s. 3441-3451
    Number of pages11 s.
    Publication formPrint - P
    Languageeng - English
    CountryUS - United States
    Keywordsfluorescent nanodiamonds ; cell immunopathology ; nanodiamond intercellular distribution ; inflammation ; inflammasome NLRP3 ; AFM ; TEM ; cathodoluminescence
    Subject RIVJA - Electronics ; Optoelectronics, Electrical Engineering
    OECD categoryNano-processes (applications on nano-scale)
    Subject RIV - cooperationInstitute of Physics - Biophysics
    R&D ProjectsEF16_019/0000760 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
    GA17-15451S GA ČR - Czech Science Foundation (CSF)
    LO1212 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
    ED0017/01/01 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
    Method of publishingLimited access
    Institutional supportUPT-D - RVO:68081731 ; FZU-D - RVO:68378271
    UT WOS000480371700011
    EID SCOPUS85068455612
    DOI10.1021/acs.molpharmaceut.9b00225
    AnnotationNanodiamonds (ND), especially fluorescent NDs, represent potentially applicable drug and probe carriers for in vitro/in vivo applications. The main purpose of this study was to relate physical-chemical properties of carboxylated NDs to their intracellular distribution and impact on membranes and cell immunity-activation of inflammasome in the in vitro THP-1 cell line model. Dynamic light scattering, nanoparticle tracking analysis, and microscopic methods were used to characterize ND particles and their intracellular distribution. Fluorescent NDs penetrated the cell membranes by both macropinocytosis and mechanical cutting through cell membranes. We proved accumulation of fluorescent NDs in lysosomes. In this case, lysosomes were destabilized and cathepsin B was released into the cytoplasm and triggered pathways leading to activation of inflammasome NLRP3, as detected in THP-1 cells. Activation of inflammasome by NDs represents an important event that could underlie the described toxicological effects in vivo induced by NDs. According to our knowledge, this is the first in vitro study demonstrating direct activation of inflammasome by NDs. These findings are important for understanding the mechanism(s) of action of ND complexes and explain the ambiguity of the existing toxicological data.
    WorkplaceInstitute of Scientific Instruments
    ContactMartina Šillerová, sillerova@ISIBrno.Cz, Tel.: 541 514 178
    Year of Publishing2020
    Electronic addresshttps://pubs.acs.org/doi/10.1021/acs.molpharmaceut.9b00225
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