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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 ASEP 0492357 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Nanodiamonds 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) ORCIDSource Title Biomaterials. - : Elsevier - ISSN 0142-9612
Roč. 176, SEP (2018), s. 106-121Number of pages 16 s. Publication form Print - P Language eng - English Country GB - United Kingdom Keywords nanodiamonds ; cell signalling ; FGF ; fibroblast growth factor ; nanotherapeutics Subject RIV JJ - Other Materials OECD category Nano-materials (production and properties) Subject RIV - cooperation Institute of Biophysics - Other Materials R&D Projects EF15_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 support UZFG-Y - RVO:67985904 ; BFU-R - RVO:68081707 ; UOCHB-X - RVO:61388963 UT WOS 000437038400010 EID SCOPUS 85049308381 DOI 10.1016/j.biomaterials.2018.05.030 Annotation The 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. Workplace Institute of Animal Physiology and Genetics Contact Jana Zásmětová, knihovna@iapg.cas.cz, Tel.: 315 639 554 Year of Publishing 2019
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