Disruption of fibrillar assemblies of L-phenylalanine using polyphenol-passivated nanocarbon as a potential therapeutic strategy against phenylketonuria.

Abstract

One of the pathological manifestations of phenylketonuria (PKU) is the formation of fibrillar assemblies of the aromatic amino acid L-phenylalanine at pathological concentrations. As a possible therapeutic strategy for PKU, we introduce a nanocarbon system passivated with polyphenol gallic acid (CNPGA), which has the ability to disrupt and inhibit the formation of fibrillar assemblies. The CNPGA was prepared using a rapid and facile microwave-assisted one-pot method from an aqueous solution of sucrose and gallic acid and fully characterized using UV-Vis, FT-IR, XRD, XPS, TEM, zeta potential and DLS measurements. The CNPGA-mediated inhibition and disruption of L-phenylalanine fibrils was examined using a thioflavin T (ThT) assay. The change in the conformation of the fibrils upon CNPGA treatment was assessed by means of circular dichroism spectroscopy. Visual analysis of the rupture of fibrillar assemblies was performed using SEM. Finally, the biocompatibility of CNPGA was evaluated in two normal cell lines, HaCaT (human epidermal keratinocyte cell line) and Vero (African green monkey kidney cell line) cells.