Drug delivery of memantine with carbon dots for Alzheimer's disease: blood-brain barrier penetration and inhibition of tau aggregation.
Alzheimer’s disease
Blood–brain barrier
Carbon dots
Memantine
Tau protein aggregation
Journal
Journal of colloid and interface science
ISSN: 1095-7103
Titre abrégé: J Colloid Interface Sci
Pays: United States
ID NLM: 0043125
Informations de publication
Date de publication:
Jul 2022
Jul 2022
Historique:
received:
17
11
2021
revised:
24
02
2022
accepted:
26
02
2022
pubmed:
8
3
2022
medline:
14
4
2022
entrez:
7
3
2022
Statut:
ppublish
Résumé
Neurofibrillary tangle, composed of aggregated tau protein, is a pathological hallmark of Alzheimer's disease (AD). The inhibition of tau aggregation is therefore an important direction for AD drug discovery. In this work, we explored the efficacy of two types of carbon dots in targeting tau aggregation, as versatile nano-carriers for the development of carbon dots (CDs)-based AD therapy. We carried out synthesis, biophysical and biochemical characterizations of two types of CDs, namely, carbon nitride dots (CNDs) and black carbon dots (B-CDs). CDs, which are biocompatible and non-toxic, were successfully conjugated with memantine hydrochloride (MH) through EDC/NHS mediated amidation reactions followed by systematic characterizations using various biophysical techniques including UV-vis spectroscopy (UV-vis), photoluminescence (PL), Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), mass spectrometry (MS), Transmission electron microscopy (TEM) and atomic force microscopy (AFM). The surface diversity along with small particle sizes of CDs allowed facile delivery of MH across the blood-brain barrier (BBB), as demonstrated using a zebrafish in vivo model. The tau aggregation inhibition experiments were conducted using the thioflavin-T (ThT) assay to identify the most effective inhibitor. The kinetics and magnitude of tau aggregation were measured in the presence of CDs, which demonstrates that both B-CDs-MH and B-CDs alone are the most effective inhibitors of tau aggregation with IC
Identifiants
pubmed: 35255395
pii: S0021-9797(22)00356-3
doi: 10.1016/j.jcis.2022.02.124
pmc: PMC9520758
mid: NIHMS1836682
pii:
doi:
Substances chimiques
tau Proteins
0
Carbon
7440-44-0
Memantine
W8O17SJF3T
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
20-31Subventions
Organisme : NIA NIH HHS
ID : RF1 AG069039
Pays : United States
Informations de copyright
Copyright © 2022 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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