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

0584540 - ÚFM 2025 RIV NL eng J - Článek v odborném periodiku
Gómez, I. J. - Křížková, P. - Dolečková, A. - Cardo, L. - Wetzl, C. - Pizúrová, Naděžda - Prato, M. - Medalová, J. - Zajíčková, L.
Multifunctional graphene quantum dots: A therapeutic strategy for neurodegenerative diseases by regulating calcium influx, crossing the blood-brain barrier and inhibiting Aβ-protein aggregation.
Applied Materials Today. Roč. 36, FEB (2024), č. článku 102072. ISSN 2352-9407. E-ISSN 2352-9407
Výzkumná infrastruktura: CzechNanoLab - 90110
Institucionální podpora: RVO:68081723
Klíčová slova: carbon nano-onions * abc transporters * nanotubes * memantine * mechanism * model * size * Carbon dots * Memantine * Protein aggregation * Blood-brain barrier * Bioimaging
Impakt faktor: 8.3, rok: 2022
Způsob publikování: Open access
https://www.sciencedirect.com/science/article/pii/S2352940724000180?via%3Dihub

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 beta-amyloid aggregates while possessing features suitable for bioimaging in various cell lines.
Trvalý link: https://hdl.handle.net/11104/0352725