Biosynthesis of Nanoparticles with Green Tea for Inhibition of β-Amyloid Fibrillation Coupled with Ligands Analysis

Int J Nanomedicine. 2024 May 14:19:4299-4317. doi: 10.2147/IJN.S451070. eCollection 2024.

Abstract

Background: Inhibition of amyloid β protein fragment (Aβ) aggregation is considered to be one of the most effective strategies for the treatment of Alzheimer's disease. (-)-Epigallocatechin-3-gallate (EGCG) has been found to be effective in this regard; however, owing to its low bioavailability, nanodelivery is recommended for practical applications. Compared to chemical reduction methods, biosynthesis avoids possible biotoxicity and cumbersome preparation processes.

Materials and methods: The interaction between EGCG and Aβ42 was simulated by molecular docking, and green tea-conjugated gold nanoparticles (GT-Au NPs) and EGCG-Au NPs were synthesized using EGCG-enriched green tea and EGCG solutions, respectively. Surface active molecules of the particles were identified and analyzed using various liquid chromatography-tandem triple quadrupole mass spectrometry methods. ThT fluorescence assay, circular dichroism, and TEM were used to investigate the effect of synthesized particles on the inhibition of Aβ42 aggregation.

Results: EGCG as well as apigenin, quercetin, baicalin, and glutathione were identified as capping ligands stabilized on the surface of GT-Au NPs. They more or less inhibited Aβ42 aggregation or promoted fibril disaggregation, with EGCG being the most effective, which bound to Aβ42 through hydrogen bonding, hydrophobic interactions, etc. resulting in 39.86% and 88.50% inhibition of aggregation and disaggregation effects, respectively. EGCG-Au NPs were not as effective as free EGCG, whereas multiple thiols and polyphenols in green tea accelerated and optimized heavy metal detoxification. The synthesized GT-Au NPs conferred the efficacy of diverse ligands to the particles, with inhibition of aggregation and disaggregation effects of 54.69% and 88.75%, respectively, while increasing the yield, enhancing water solubility, and decreasing cost.

Conclusion: Biosynthesis of nanoparticles using green tea is a promising simple and economical drug-carrying approach to confer multiple pharmacophore molecules to Au NPs. This could be used to design new drug candidates to treat Alzheimer's disease.

Keywords: (-)-epigallocatechin-3-gallate; amyloid β protein; gold nanoparticles; green synthesis; green tea; liquid chromatography tandem triple quadrupole mass spectrometry.

MeSH terms

  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / metabolism
  • Amyloid beta-Peptides* / antagonists & inhibitors
  • Amyloid beta-Peptides* / metabolism
  • Catechin* / analogs & derivatives
  • Catechin* / chemistry
  • Catechin* / pharmacology
  • Gold* / chemistry
  • Humans
  • Ligands
  • Metal Nanoparticles* / administration & dosage
  • Metal Nanoparticles* / chemistry
  • Molecular Docking Simulation*
  • Peptide Fragments* / antagonists & inhibitors
  • Peptide Fragments* / chemistry
  • Protein Aggregates / drug effects
  • Tea* / chemistry

Substances

  • epigallocatechin gallate
  • amyloid beta-protein (1-42)

Grants and funding

This work was financially supported by the National Key Research and Development Program of China (2023YFC3403000 and 2021YFC2401100) and Tianjin Provincial Key Research and Development Program, China (22YFYSHZ00140).