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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Authors

GOMEZ PEREZ Inmaculada Jennifer KŘÍŽKOVÁ Petra DOLEČKOVÁ Anna CARDO Lucía WETZL Cecilia PIZÚROVÁ Naděžda PRATO Maurizio MEDALOVÁ Jiřina ZAJÍČKOVÁ Lenka

Year of publication 2024
Type Article in Periodical
Magazine / Source Applied Materials Today
MU Faculty or unit

Faculty of Science

Citation
web https://www.sciencedirect.com/science/article/pii/S2352940724000180
Doi http://dx.doi.org/10.1016/j.apmt.2024.102072
Keywords Bioimaging; Blood-brain barrier; Carbon dots; Memantine; Protein aggregation
Description 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 ß-amyloid aggregates while possessing features suitable for bioimaging in various cell lines.
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