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

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

Mai Zhang  1 , Yan Li  1   2 , Chunli Han  3 , Shiying Chu  1 , Peng Yu  1 , Wenbo Cheng  1   2
Affiliations

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

Mai Zhang et al. Int J Nanomedicine. .

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.

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Conflict of interest statement

The authors declare no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Diagram of green tea biosynthesis of Au NPs with ligands identified by mass spectrometry and inhibition of Aβ fibrillation.
Figure 2
Figure 2
Three-dimensional structures and molecular docking simulation of Aβ42 and EGCG. The initial conformation of Aβ42 (a) and EGCG (b). (c) A graphical representation of the molecular surface of the EGCG docking with Aβ42. (d) Interfacial forces between Aβ42 and EGCG. The distance between the two atoms is less than 4 Å, indicated by the green solid line. EGCG was shown in cyan, and Aβ42 in beige. Oxygen atoms were labeled in red and nitrogen atoms in blue. The atomic notation were provided by Chimera and follow the PDB convention.
Figure 3
Figure 3
Characterization of synthesized GT-Au NPs. (a) Appearance of the solution and precipitate after the reaction. The ratio of green tea extract to HAuCl4 was 1:10 (i, v), 1:5 (ii, vi), 3:10 (iii, vii) and 2:5 (iv, viii). UV-visible absorption curves (b) and TEM (c) of purified GT-Au NPs. (d) Assessment of size distribution for GT-Au NPs measured by DLS. XRD pattern (e), full scan XPS survey spectrum (f), and FT-IR spectrum (g) of GT-Au NPs.
Figure 4
Figure 4
Methodology development for EGCG detection by mass spectrometry. (a) Chromatographic signals of EGCG and internal standard (quercetin, H) in standard solutions. (b) Linear standard curve and correlation coefficient. (c) Signal-to-noise (S/N) ratio at the lower limit of quantification.
Figure 5
Figure 5
EGCG detection by mass spectrometry in the post-reaction supernatant (a) and in the GT-Au NPs precipitate (b). The control group was supplemented with water instead of HAuCl4.
Figure 6
Figure 6
Effect of GT-Au NPs on Aβ42 fibrillization in vitro. ThT fluorescence assay on the aggregation inhibition (a) and disaggregation (b) of Aβ42 in the absence and presence of GT-Au NPs. (c) CD spectra of Aβ42 (40 μM) in the absence and presence of GT-Au NPs after co-incubation for 72 h. (d) Analysis of protein secondary structure. (e) Effect of GT-Au NPs with different synthesis times on aggregation inhibition (left axis) and degradation (right axis) of Aβ42. (f) Effect of GT-Au NPs with different substrate concentrations on aggregation inhibition (left axis) and degradation (right axis) of Aβ42.
Figure 7
Figure 7
Comparison of GT-Au NPs and EGCG-Au NPs in terms of properties and the effects on Aβ42 fibrillation with ligand analysis. Mass spectrometry methodology development of apigenin (A), baicalin (LIN), quercetin (Q) and glutathione (GSH) in the matrix of supernatant (a) and GT-Au NPs precipitate (b). Detection of A, LIN, Q and GSH in GT-Au NPs precipitates (c) or post-reaction supernatants (d). (e) The effects of EGCG-Au NPs, GT-Au NPs and various small molecule ligands on Aβ42 fibrillation. (f) Comparison of the appearance, yield and dispersion in water of EGCG-Au NPs and GT-Au NPs. TEM images of Aβ42 in the absence (g) and presence of EGCG-Au NPs (h) or GT-Au NPs (i) after co-incubation for 24 h.
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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).

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