期刊
JOURNAL OF COLLOID AND INTERFACE SCIENCE
卷 617, 期 -, 页码 20-31出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.jcis.2022.02.124
关键词
Carbon dots; Blood-brain barrier; Memantine; Tau protein aggregation; Alzheimer's disease
资金
- National Science Foundation [1809060, 2041413]
- University of Miami, USA
- NI [AG069039]
This study explored the efficacy of two types of carbon dots as nano-carriers for Alzheimer's disease therapy. The carbon dots successfully inhibited the aggregation of tau protein, demonstrating their potential for drug delivery in Alzheimer's treatment. These findings have significant implications for enhancing the delivery of drugs to target Alzheimer's pathology in the brain.
Neurofibrillary tangle, composed of aggregated tau protein, isa pathological hallmark of Alzheimer's dis-ease (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, bio-physical 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 sys-tematic 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 inhi-bition experiments were conducted using the thioflavin-T (ThT) assay to identify the most effective inhi-bitor. 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 lg/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. (c) 2022 Elsevier Inc. All rights reserved.
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