Uniform, Polycrystalline, and Thermostable Piperine-Coated Gold Nanoparticles to Target Insulin Fibril Assembly

Abstract

Because the process of insulin fibril assembly is linked to a multitude of medical problems, finding effective and biocompatible inhibitors against such an aggregation process could be beneficial. Targeting the aggregation-prone residues of insulin may perhaps work as an effective strategy to prevent the onset of insulin fibril assembly. In this work, we have synthesized uniform sized, thermostable gold nanoparticles (AuNPs piperine ) surface-functionalized with piperine to target amyloid-prone residues of insulin. We found that the process of both spontaneous and seed-induced amyloid formation of insulin was strongly inhibited in the presence of AuNPs piperine . Surface functionalization of piperine was found to be critical to its inhibition effect because no such effect was observed for free piperine as well as for uncoated control gold nanoparticles. Fluorescence quenching data revealed binding of AuNPs piperine with insulin's native structure which was further validated by docking studies that predicted viable H-bond and CH-π interactions between piperine and key aggregation-prone residues of insulin's B-chain. Our hemolysis assay studies further confirmed that these piperine coated nanoparticles were hemocompatible. Data obtained from both experimental and computational studies suggest that the retention of native structure of insulin and the ability of the piperine molecule to interact with the aggregation-prone residues of insulin are the key factors for the inhibition mechanism. The findings of this work may help in the development of nanoparticle-based formulations to prevent medical problems linked to insulin aggregation.

Synergistic Effects of Curcumin and Piperine as Potent Acetylcholine and Amyloidogenic Inhibitors With Significant Neuroprotective Activity in SH-SY5Y Cells via Computational Molecular Modeling and in vitro Assay

“…But from our data, piperine might play a role in disintegrating the Aβ fibril formation. Recent studies reported that indirect involvement of piperine-coated gold formation was able to inhibit amyloid-prone residues of insulin (Anand et al, 2017, 2018). They found that the process of both spontaneous and seed-induced (misfolded protein aggregates) amyloid formation of insulin was strongly inhibited in the presence of piperine-coated gold nanoparticles.…”

Metal nanoparticles synthesis through natural phenolic acids

“…Although the UV–Vis absorption spectroscopy technique has verified the capability of phenolic acids to reduce metal ions, this method could not verify the attachment of phenolic acids to the surface of the synthesised NPs [91]. On the other hand, it is possible to detect characteristic absorbance peaks for capsaicin, cinnamic acid, gallic acid, salicylic acid, and other phenolic acids attached to the surfaces of metal NPs using Fourier‐transform infrared spectroscopy technique [50, 66, 68, 92]. Some other spectroscopic techniques have also been used for studying phenolic acid absorption on the surface of metal NPs.…”

An overview of functional nanoparticles as novel emerging antiviral therapeutic agents

“…Gold nanoparticles, one of the earliest synthesized nanomaterials with superior electric, optical and mechanical properties [65,66], have attracted attention in nanodiagnostic and nanomedical applications due to their exquisite quantum size effect, surface effect, and macroscopic quantum tunneling effect. Thus far, various methods for the preparation of gold nanoparticles have been reported and reviewed [67][68][69], and many small molecule, DNA sequence, protein, bacterial, and virus detection methods have been developed based on gold nanoparticles. For example, Mirkin and his coworkers are the first team dedicated to the preparation and application of gold nanoparticles in biology and medicine, and they systematically reviewed the synthesis, modification and application of gold nanoparticles [70].…”