Functionalized gold and silver nanoparticles modulate amyloid fibrillation, defibrillation and cytotoxicity of lysozyme via altering protein surface character

Abstract

Although small size and tunable surface properties of metal nanoparticles such as gold and silver (AuNP, AgNP) have been explored in many biomedical applications, their effect on protein amyloid fibrillation and defibrillation has partly been investigated. Here, we synthesized starch and polyethylene glycol (PEG) functionalized AuNP and AgNP and explored their effect on amyloid fibrillation, defibrillation and cytotoxicity of hen egg white lysozyme (HEWL) as a model protein. Our experimental results revealed that lower concentration of PEGylated NPs (0.1–1 μM) exhibited higher anti-amyloid activity than starch capped NPs while higher concentration (5–20 μM), however showed nearly equal effect for both. Such inhibiting properties were attributed to the modulation of surface charge, surface hydrophobicity and capping agent of NPs. We further observed NP-mediated profound inhibition of fibril formation only during nucleation phase of amyloid growth. Defibrillation study of HEWL amyloid further revealed that starch functionalized NPs can defibrillate more efficiently than PEGylated NPs. When cytotoxicity of amyloid was assessed in mice neural (N2a) and human keratinocytes cells (HaCaT), amyloid samples prepared with NPs showed much reduced cytotoxicity compared to the untreated sample. Experimental results further showed that the reduction of cytotoxicity by NPs was mediated via preventing free radical generation. Overall, we concluded that appropriate selection of core material, surface modification and administration time of NP might be the key in inhibiting amyloid fibrillation and triggering defibrillation process of HEWL effectively.