Multifunctional graphene quantum dots: A therapeutic strategy for neurodegenerative diseases by regulating calcium influx, crossing the blood-brain barrier and inhibiting Aβ-protein aggregation

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Abstract

Multifunctional nanoparticles could be the hallmark for the treatment of neurodegenerative diseases. Dissociation of protein aggregates causing neuronal damage and transfer of specific drugs which can downregulate neuronal excitotoxicity by inhibiting glutamatergic N-Methyl-d-Aspartate-receptors (NMDA) and then reducing calcium influx are among the main factors to consider for proper therapy. Here, we present a multiplatform based on nitrogen-doped graphene quantum dots (NGQDs) with such functionalities. The NGQDs were functionalized with Memantine, the clinically used drug, via covalent and non-covalent coupling, and we confirmed that the pharmaceutical activity was not altered. Apart from that, using xCELLigence technology and flow cytometric analysis of ABC transporter function, we uncovered that the ABC transporters of the blood-brain barrier (BBB) do not affect the ability of NGQD to cross BBB. Surprisingly, this study found that NGQDs have an inhibitory effect on NMDA receptors, thus supporting the action of Memantine. Moreover, NGQDs and their derivatives demonstrated the potential to dissociate β-amyloid aggregates while possessing features suitable for bioimaging in various cell lines.

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Authors:

I. Jennifer Gomez* (a,b), Petra Křížková (c,d), Anna Dolečková (c,d), Lucía Cardo (d), Cecilia Wetzl (d,e), Naděžda Pizúrová (f), Maurizio Prato (d,g,h), Jiřina Medalová* (c), Lenka Zajíčková* a,i

*corresponding authors

Affiliation:

aDepartment of Condensed Matter Physics, Faculty of Science, Masaryk University, 61137 Brno, Czech Republic

bCentro Interdisciplinar de Química e Bioloxía (CICA), Universidade da Coruña, Rúa As Carballeiras, 15071 A Coruña, Spain

cDepartment of Experimental Biology, Faculty of Science, Masaryk University, 62500 Brno, Czech Republic

dCenter for Cooperative Research in Biomaterials (CIC biomaGUNE), Basque Research and Technology Alliance (BRTA), 20014 Donostia-San Sebastián, Spain

eUniversity of the Basque Country, UPV-EHU, 20018 San Sebastián, Spain

fInstitute of Physics of Materials, Czech Academy of Sciences, 61662 Brno, Czech Republic

gDepartment of Chemical and Pharmaceutical Sciences, University of Trieste, 34127 Trieste, Italy

hIkerbasque, Basque Foundation for Science, 48013 Bilbao, Spain

iCentral European Institute of Technology – CEITEC, Brno University of Technology, 61200 Brno, Czech Republic