Examining the inhibitory potency of metal polyphenolic network-coated silver nanoparticles against amyloid fibrillogenesis of lysozyme

There are currently over forty degenerative diseases that are correlated with abnormal accumulation of peptide/ protein aggregates in the human body, such as Alzheimer's disease. Due to their unique physiochemical properties (e.g., small size, large surface-to-volume ratio, and facile surface modification), silver nanoparticles (AgNPs) have been considered potential substrates for designing inhibitors against amyloid fibrillogenesis. Metal polyphenolic network (MPN) that combines the characteristics of organic and inorganic components has been used to suppress amyloid fibril formation. This study is aimed at investigating the effects of MPN-coated AgNPs (MPN-AgNPs) on the in vitro amyloid fibrillogenesis of hen lysozyme (HEWL). The two types of MPN-AgNPs (Zn/MPN-AgNPs and Co/MPN-AgNPs) were synthesized through chemical reduction and metal chelation, and their particle sizes were determined to be in the range of 40-60 nm. The characterization of MPN-AgNPs by zeta-potential and transmission electron microscopy showed that the MPN-AgNPs had negative surface charge and spherical-shaped morphology. Furthermore, the elemental analysis demonstrated that the MPN was uniformly coated on the surface of AgNPs. The thioflavin T fluorescence results revealed that the Co/MPN-AgNPs showed a better percent of inhibition compared to Zn/MPN-AgNPs and TA-AgNPs. The kinetics data of amyloid fibril formation in the presence of MPN-AgNPs were analyzed using the sigmoidal curve, showing that the MPN-AgNPs reduced fibril growth rate and prolonged lag time. Our findings also demonstrated that MPN-AgNPs could effectively suppress HEWL aggregation upon binding to aggregation-prone regions. The quenching of intrinsic fluorescence of HEWL by MPN-AgNPs was found to be a static type. Moreover, the fluorescence quenching data were analyzed using the modified Stern-Volmer equation to determine the number of binding sites. Notably, our findings indicated that the binding between HEWL and MPN-AgNPs was mainly governed by hydrophobic interaction. This work offers an excellent example of utilizing MPN-based materials as antiaggregating/anti-fibrillogenic nano-drugs for the treatment of amyloidosis.