Carbon dots as dual inhibitors of tau and amyloid-beta aggregation for the treatment of Alzheimer's disease.

Autor: Zhang W; Department of Chemistry, University of Miami, Coral Gables, FL 33146, USA., Smith N; Department of Biological Sciences, Rensselaer Polytechnic Institute, NY 12180, USA., Zhou Y; Department of Chemistry, University of Miami, Coral Gables, FL 33146, USA; Department of Biological Sciences, Florida International University, Miami, FL 33199, USA., McGee CM; Department of Chemistry, University of Miami, Coral Gables, FL 33146, USA., Bartoli M; Department of Applied Science and Technology, Politecnico di Torino, Italy; Center for Sustainable Future Technologies (CSFT), Istituto Italiano di Technologia (IIT), Via Livorno 60, 10144 Turin, Italy., Fu S; Department of Chemistry, University of Miami, Coral Gables, FL 33146, USA., Chen J; Department of Chemistry, University of Miami, Coral Gables, FL 33146, USA., Domena JB; Department of Chemistry, University of Miami, Coral Gables, FL 33146, USA., Joji A; Department of Chemistry, University of Miami, Coral Gables, FL 33146, USA., Burr H; Department of Biological Sciences, Rensselaer Polytechnic Institute, NY 12180, USA., Lv G; Department of Biochemistry, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA., Cilingir EK; Department of Chemistry, University of Miami, Coral Gables, FL 33146, USA., Bedendo S; Department of Applied Science and Technology, Politecnico di Torino, Italy., Claure ML; Department of Chemistry, University of Miami, Coral Gables, FL 33146, USA., Tagliaferro A; Department of Applied Science and Technology, Politecnico di Torino, Italy., Eliezer D; Department of Biochemistry, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA., Veliz EA; Department of Natural Sciences, Miami Dade Collage, Miami, FL 33132, USA., Zhang F; Department of Chemistry, University of Miami, Coral Gables, FL 33146, USA., Wang C; Department of Biological Sciences, Rensselaer Polytechnic Institute, NY 12180, USA. Electronic address: wangc5@rpi.edu., Leblanc RM; Department of Chemistry, University of Miami, Coral Gables, FL 33146, USA. Electronic address: rml@miami.edu.
Jazyk: angličtina
Zdroj: Acta biomaterialia [Acta Biomater] 2024 Jul 15; Vol. 183, pp. 341-355. Date of Electronic Publication: 2024 Jun 05.
DOI: 10.1016/j.actbio.2024.06.001
Abstrakt: Alzheimer's disease (AD) is the most common form of senile dementia, presenting a significant challenge for the development of effective treatments. AD is characterized by extracellular amyloid plaques and intraneuronal neurofibrillary tangles. Therefore, targeting both hallmarks through inhibition of amyloid beta (Aβ) and tau aggregation presents a promising approach for drug development. Carbon dots (CD), with their high biocompatibility, minimal cytotoxicity, and blood-brain barrier (BBB) permeability, have emerged as promising drug nanocarriers. Congo red, an azo dye, has gathered significant attention for inhibiting amyloid-beta and tau aggregation. However, Congo red's inability to cross the BBB limits its potential to be used as a drug candidate for central nervous system (CNS) diseases. Furthermore, current studies only focus on using Congo red to target single disease hallmarks, without investigating dual inhibition capabilities. In this study, we synthesized Congo red-derived CD (CRCD) by using Congo red and citric acid as precursors, resulting in three variants, CRCD1, CRCD2 and CRCD3, based on different mass ratios of precursors. CRCD2 and CRCD3 exhibited sustained low cytotoxicity, and CRCD3 demonstrated the ability to traverse the BBB in a zebrafish model. Moreover, thioflavin T (ThT) aggregation assays and AFM imaging revealed CRCD as potent inhibitors against both tau and Aβ aggregation. Notably, CRCD1 emerged as the most robust inhibitor, displaying IC 50 values of 0.2 ± 0.1 and 2.1 ± 0.5 µg/mL against tau and Aβ aggregation, respectively. Our findings underscore the dual inhibitory role of CRCD against tau and Aβ aggregation, showcasing effective BBB penetration and positioning CRCD as potential nanodrugs and nanocarriers for the CNS. Hence, CRCD-based compounds represent a promising candidate in the realm of multi-functional AD therapeutics, offering an innovative formulation component for future developments in this area. STATEMENT OF SIGNIFICANCE: This article reports Congo red-derived carbon dots (CRCD) as dual inhibitors of tau and amyloid-beta (Aβ) aggregation for the treatment of Alzheimer's disease (AD). The CRCD are biocompatible and show strong fluorescence, high stability, the ability to cross the blood-brain barrier, and the function of addressing two major pathological features of AD.
Competing Interests: Declaration of competing interest The authors declare no competing financial interest.
(Copyright © 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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