Title
Uniform, polycrystalline and thermostable piperine-coated gold nanoparticles to target insulin fibril assembly
Author
Bibin Gnanadhason Anand, Dolat Singh Shekhawat, Kriti Dubey, Karunakar Kar
Year
2017
Journal
ACS Biomaterials Science & Engineering
Abstract
Since the process of insulin fibril assembly is linked to a multitude of medical problems, finding effective and biocompatible inhibitors against such 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 (AuNPspiperine) 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 AuNPspiperine. 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 AuNPspiperine with insulin’s native structure which was further validated by docking studies that predicted viable H-bond and CH- 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.
Instrument
J-815
Keywords
Circular dichroism, Secondary structure, Nanostructures, Aggregation, Biochemistry, Materials