Zn‐Conjugated Graphene Oxide Nanoparticle–Mediated Inhibition of Human Islet Amyloid Polypeptide (hIAPP) Amyloid Formation: Their Synergistic Effects

Human islet amyloid polypeptide (hIAPP) oligomers, formed through an accumulation pathway, are toxic to insulin‐secreting pancreatic β‐cells and are considered to contribute for β‐cell death and insulin deficiency commonly observed in type 2 diabetes (T2D) patients. In this study, we investigated and compared the antiaggregation effects of several nanoparticles (NPs) including zinc acetate, graphene oxide (GO), and zinc‐conjugated GO (GO–NH 2 –Zn) on their interactions with hIAPP. For this purpose, GO was purchased and subsequently conjugated with zinc acetate. Recombinant hIAPP was produced and its amyloidogenic behavior was evaluated in the presence of different concentrations of GO, zinc acetate, and GO–NH 2 –Zn. Thioflavin T (ThT) fluorescence spectroscopy was applied to examine the amyloid behavior of the protein. Additionally, the transmission electron microscopy (TEM) images of amyloid particles alone and in the presence of GO–NH 2 –Zn NP were recorded. A cell toxicity assay revealed these NPs protected insulin‐secreting NIT‐1 pancreatic β‐cells from hIAPP–induced toxicity. TEM images and ThT fluorescence spectra confirmed the reduction in hIAPP aggregation in the presence of GO–NH 2 –Zn. Our results clearly demonstrated that both zinc acetate and GO extended the lag‐phase latency to form amyloid fibrils, while GO–NH 2 –Zn exerted a synergistic inhibitory effect on fibril formation. Furthermore, when GO–NH 2 –Zn was incubated with fetal bovine serum (FBS) to form a hard corona mimicking in vivo circumstances, it effectively prevented the formation of amyloid as expected. Our study suggests that the GO–NH 2 –Zn, as an antiaggregation NP, has potential for use in designing new nanomedicine agents to inhibit hIAPP fibril formation and treat T2D disease.