J 2018

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

BÁLEK, Lukáš, Marcela BUCHTOVÁ, Michaela BOSÁKOVÁ, Miroslav VAŘECHA, Silvie TRANTÍRKOVÁ et. al.

Basic information

Original name

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

Authors

BÁLEK, Lukáš (203 Czech Republic, belonging to the institution), Marcela BUCHTOVÁ (203 Czech Republic, belonging to the institution), Michaela BOSÁKOVÁ (203 Czech Republic, belonging to the institution), Miroslav VAŘECHA (203 Czech Republic, belonging to the institution), Silvie TRANTÍRKOVÁ (203 Czech Republic, belonging to the institution), Iva GUDERNOVÁ (203 Czech Republic, belonging to the institution), Iva VESELÁ (203 Czech Republic, belonging to the institution), Jan HAVLIK (203 Czech Republic), Jitka NEBURKOVA (203 Czech Republic), Stuart TURNER (56 Belgium), Mateusz Adam KRZYSCIK (616 Poland), Malgorzata ZAKRZEWSKA (56 Belgium), Lars KLIMASCHEWSKI (40 Austria), Peter CLAUS (276 Germany), Lukáš TRANTÍREK (203 Czech Republic, belonging to the institution), Petr CIGLER (203 Czech Republic) and Pavel KREJČÍ (203 Czech Republic, guarantor, belonging to the institution)

Edition

Biomaterials, OXFORD, ELSEVIER SCI LTD, 2018, 0142-9612

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30404 Biomaterials

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 10.273

RIV identification code

RIV/00216224:14110/18:00101655

Organization unit

Faculty of Medicine

UT WoS

000437038400010

Keywords in English

Nanodiamonds; Cell signalling; FGF; Fibroblast growth factor; Nanotherapeutics

Tags

International impact, Reviewed
Změněno: 20/4/2022 12:40, Mgr. Marie Šípková, DiS.

Abstract

V originále

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.

Links

GA17-09525S, research and development project
Name: Neobvyklé signální dráhy lidských receptorových tyrozinových kináz
Investor: Czech Science Foundation
GA17-12075S, research and development project
Name: Polymorfní G-quadruplexy v promotorových oblastech genů
Investor: Czech Science Foundation
LH15231, research and development project
Name: Nové mechanismy vzniku fatálních kostních ciliopatií u člověka
Investor: Ministry of Education, Youth and Sports of the CR
LQ1601, research and development project
Name: CEITEC 2020 (Acronym: CEITEC2020)
Investor: Ministry of Education, Youth and Sports of the CR
NV15-33232A, research and development project
Name: Identifikace nových možností léčby achondroplásie prostřednictvím analýzy interakce FGFR3 a adaptérového proteinu Frs2
NV15-34405A, research and development project
Name: Identifikace nových možností léčby chronické myeloidní leukémie pomocí systematické analýzy interaktomu proteinu BCR-ABL