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@article{1490507,
author = {Bálek, Lukáš and Buchtová, Marcela and Bosáková, Michaela and Vařecha, Miroslav and Trantírková, Silvie and Gudernová, Iva and Veselá, Iva and Havlik, Jan and Neburkova, Jitka and Turner, Stuart and Krzyscik, Mateusz Adam and Zakrzewska, Malgorzata and Klimaschewski, Lars and Claus, Peter and Trantírek, Lukáš and Cigler, Petr and Krejčí, Pavel},
article_location = {OXFORD},
article_number = {SEP 2018},
doi = {http://dx.doi.org/10.1016/j.biomaterials.2018.05.030},
keywords = {Nanodiamonds; Cell signalling; FGF; Fibroblast growth factor; Nanotherapeutics},
language = {eng},
issn = {0142-9612},
journal = {Biomaterials},
title = {Nanodiamonds as "artificial proteins": Regulation of a cell signalling system using low nanomolar solutions of inorganic nanocrystals},
url = {https://www.sciencedirect.com/science/article/pii/S0142961218303739?via%3Dihub},
volume = {176},
year = {2018}
}
TY - JOUR
ID - 1490507
AU - Bálek, Lukáš - Buchtová, Marcela - Bosáková, Michaela - Vařecha, Miroslav - Trantírková, Silvie - Gudernová, Iva - Veselá, Iva - Havlik, Jan - Neburkova, Jitka - Turner, Stuart - Krzyscik, Mateusz Adam - Zakrzewska, Malgorzata - Klimaschewski, Lars - Claus, Peter - Trantírek, Lukáš - Cigler, Petr - Krejčí, Pavel
PY - 2018
TI - Nanodiamonds as "artificial proteins": Regulation of a cell signalling system using low nanomolar solutions of inorganic nanocrystals
JF - Biomaterials
VL - 176
IS - SEP 2018
SP - 106-121
EP - 106-121
PB - ELSEVIER SCI LTD
SN - 01429612
KW - Nanodiamonds
KW - Cell signalling
KW - FGF
KW - Fibroblast growth factor
KW - Nanotherapeutics
UR - https://www.sciencedirect.com/science/article/pii/S0142961218303739?via%3Dihub
N2 - 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. (C) 2018 The Authors. Published by Elsevier Ltd.
ER -
BÁLEK, Lukáš, Marcela BUCHTOVÁ, Michaela BOSÁKOVÁ, Miroslav VAŘECHA, Silvie TRANTÍRKOVÁ, Iva GUDERNOVÁ, Iva VESELÁ, Jan HAVLIK, Jitka NEBURKOVA, Stuart TURNER, Mateusz Adam KRZYSCIK, Malgorzata ZAKRZEWSKA, Lars KLIMASCHEWSKI, Peter CLAUS, Lukáš TRANTÍREK, Petr CIGLER and Pavel KREJČÍ. Nanodiamonds as ''artificial proteins'': Regulation of a cell signalling system using low nanomolar solutions of inorganic nanocrystals. \textit{Biomaterials}. OXFORD: ELSEVIER SCI LTD, 2018, vol.~176, SEP 2018, p.~106-121. ISSN~0142-9612. Available from: https://dx.doi.org/10.1016/j.biomaterials.2018.05.030.
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