Biosynthesis of Nanoparticles with Green Tea for Inhibition of [beta]-Amyloid Fibrillation Coupled with Ligands Analysis

Background: Inhibition of amyloid [beta] protein fragment (A[beta]) 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 A[beta]42 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 A[beta]42 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 A[beta]42 aggregation or promoted fibril disaggregation, with EGCG being the most effective, which bound to A[beta]42 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: gold nanoparticles, green synthesis, (-)-epigallocatechin-3- gallate, liquid chromatography tandem triple quadrupole mass spectrometry, amyloid [beta] protein, green tea