Drug delivery of memantine with carbon dots for Alzheimer's disease: blood–brain barrier penetration and inhibition of tau aggregation

Wei Zhang, Nabin Kandel, Yiqun Zhou, Nathan Smith, Braulio C.L.B. Ferreira, Miranda Perez, Matteo L. Claure, Keenan J. Mintz, Chunyu Wang, Roger M. Leblanc

Research output: Contribution to journalArticlepeer-review

Abstract

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 IC50 values of 1.5 ± 0.3 and 1.6 ± 1.5 μg/mL, respectively. Taken together, our findings hold therapeutic significance to enhance the efficient delivery of MH to target AD pathology in the brain for improved efficacy.

Original languageEnglish (US)
Pages (from-to)20-31
Number of pages12
JournalJournal of Colloid And Interface Science
Volume617
DOIs
StatePublished - Jul 2022
Externally publishedYes

Keywords

  • Alzheimer's disease
  • Blood–brain barrier
  • Carbon dots
  • Memantine
  • Tau protein aggregation

ASJC Scopus subject areas

  • Electronic, Optical and Magnetic Materials
  • Biomaterials
  • Surfaces, Coatings and Films
  • Colloid and Surface Chemistry

Fingerprint

Dive into the research topics of 'Drug delivery of memantine with carbon dots for Alzheimer's disease: blood–brain barrier penetration and inhibition of tau aggregation'. Together they form a unique fingerprint.

Cite this