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Nanodiamonds as „artificial proteins“: Regulation of a cell signalling system using low nanomolar solutions of inorganic nanocrystals

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    SYSNO ASEP0492357
    Document TypeJ - Journal Article
    R&D Document TypeJournal Article
    Subsidiary JČlánek ve WOS
    TitleNanodiamonds as „artificial proteins“: Regulation of a cell signalling system using low nanomolar solutions of inorganic nanocrystals
    Author(s) Bálek, L. (CZ)
    Buchtová, Marcela (UZFG-Y) RID, ORCID
    Kunová Bosáková, M. (CZ)
    Vařecha, M. (CZ)
    Foldynová-Trantírková, Silvie (BFU-R) ORCID
    Gudernová, I. (CZ)
    Veselá, I. (CZ)
    Havlík, Jan (UOCHB-X) RID
    Neburková, Jitka (UOCHB-X) RID, ORCID
    Turner, S. (BE)
    Krzyscik, M. A. (PL)
    Zakrzewska, M. (PL)
    Klimaschewski, L. (AT)
    Claus, P. (DE)
    Trantírek, L. (CZ)
    Cígler, Petr (UOCHB-X) RID, ORCID
    Krejčí, Pavel (UZFG-Y) ORCID
    Source TitleBiomaterials. - : Elsevier - ISSN 0142-9612
    Roč. 176, SEP (2018), s. 106-121
    Number of pages16 s.
    Publication formPrint - P
    Languageeng - English
    CountryGB - United Kingdom
    Keywordsnanodiamonds ; cell signalling ; FGF ; fibroblast growth factor ; nanotherapeutics
    Subject RIVJJ - Other Materials
    OECD categoryNano-materials (production and properties)
    Subject RIV - cooperationInstitute of Biophysics - Other Materials
    R&D ProjectsEF15_003/0000477 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
    GA17-09525S GA ČR - Czech Science Foundation (CSF)
    GA17-12075S GA ČR - Czech Science Foundation (CSF)
    EF16_019/0000729 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
    Institutional supportUZFG-Y - RVO:67985904 ; BFU-R - RVO:68081707 ; UOCHB-X - RVO:61388963
    UT WOS000437038400010
    EID SCOPUS85049308381
    DOI10.1016/j.biomaterials.2018.05.030
    AnnotationThe blocking of specific protein-protein interactions using nanoparticles is an emerging alternative to small molecule-based therapeutic interventions. However, the nanoparticles designed as „artificial proteins“ generally require modification of their surface with (bio)organic molecules and/or polymers to ensure their selectivity and specificity of action. Here, we show that nanosized diamond crystals (nanodiamonds, NDs) without any synthetically installed (bio)organic interface enable the specific and efficient targeting of the family of extracellular signalling molecules known as fibroblast growth factors (FGFs). We found that low nanomolar solutions of detonation NDs with positive-potential strongly associate with multiple FGF ligands present at sub-nanomolar concentrations and effectively neutralize the effects of FGF signalling in cells without interfering with other growth factor systems and serum proteins unrelated to FGFs. We identified an evolutionarily conserved FGF recognition motif, 17 amino acids long, that contributes to the selectivity of the ND-FGF interaction. In addition, we inserted this motif into a de novo constructed chimeric protein, which significantly improved its interaction with NDs. We demonstrated that the interaction of NDs, as purely inorganic nanoparticles, with proteins can mitigate pathological FGF signalling and promote the restoration of cartilage growth in a mouse limb explant model. Based on our observations, we foresee that NDs may potentially be applied as nano therapeutics to neutralize disease-related activities of FGFs in vivo.
    WorkplaceInstitute of Animal Physiology and Genetics
    ContactJana Zásmětová, knihovna@iapg.cas.cz, Tel.: 315 639 554
    Year of Publishing2019
Number of the records: 1  

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