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

L. Balek, M. Buchtova, M. Kunova Bosakova, M. Varecha, S. Foldynova-Trantirkova, I. Gudernova, I. Vesela, J. Havlik, J. Neburkova, S. Turner, MA. Krzyscik, M. Zakrzewska, L. Klimaschewski, P. Claus, L. Trantirek, P. Cigler, P. Krejci,

. 2018 ; 176 (-) : 106-121. [pub] 20180521

Jazyk angličtina Země Nizozemsko

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc19045422

Grantová podpora
NV15-33232A MZ0 CEP - Centrální evidence projektů
NV15-34405A MZ0 CEP - Centrální evidence projektů

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 ζ-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 nanotherapeutics to neutralize disease-related activities of FGFs in vivo.

Citace poskytuje Crossref.org

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$a Kunova Bosakova, Michaela $u Department of Biology, Faculty of Medicine, Masaryk University, 62500, Brno, Czech Republic; International Clinical Research Center, St. Anne's University Hospital, 65691, Brno, Czech Republic.
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$a Varecha, Miroslav $u Department of Biology, Faculty of Medicine, Masaryk University, 62500, Brno, Czech Republic; International Clinical Research Center, St. Anne's University Hospital, 65691, Brno, Czech Republic.
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$a Foldynova-Trantirkova, Silvie $u Central European Institute of Technology, Masaryk University, 62500, Brno, Czech Republic; Institute of Biophysics of the CAS, 61265, Brno, Czech Republic.
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$a Gudernova, Iva $u Department of Biology, Faculty of Medicine, Masaryk University, 62500, Brno, Czech Republic.
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$a Havlik, Jan $u Institute of Organic Chemistry and Biochemistry of the CAS, 16610, Prague, Czech Republic; Faculty of Science, Charles University, 12840, Prague, Czech Republic.
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$a Neburkova, Jitka $u Institute of Organic Chemistry and Biochemistry of the CAS, 16610, Prague, Czech Republic; First Faculty of Medicine, Charles University, 12108, Prague, Czech Republic.
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$a Turner, Stuart $u EMAT, University of Antwerp, Groenenborgerlaan 171, B-2020, Antwerp, Belgium.
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$a Krzyscik, Mateusz Adam $u Department of Protein Engineering, Faculty of Biotechnology, University of Wroclaw, 50-383, Wroclaw, Poland.
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$a Zakrzewska, Malgorzata $u Department of Protein Engineering, Faculty of Biotechnology, University of Wroclaw, 50-383, Wroclaw, Poland.
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$a Klimaschewski, Lars $u Division of Neuroanatomy, Medical University of Innsbruck, A-6020, Innsbruck, Austria.
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$a Claus, Peter $u Institute of Neuroanatomy and Cell Biology, Hannover Medical School, 30625, Hannover, Germany.
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$a Trantirek, Lukas $u Central European Institute of Technology, Masaryk University, 62500, Brno, Czech Republic.
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$a Cigler, Petr $u Institute of Organic Chemistry and Biochemistry of the CAS, 16610, Prague, Czech Republic. Electronic address: cigler@uochb.cas.cz.
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