Graphene quantum dots against human IAPP aggregation and toxicity in vivo

Nanoscale. 2018 Nov 1;10(42):19995-20006. doi: 10.1039/c8nr07180b.

Abstract

The development of biocompatible nanomaterials has become a new frontier in the detection, treatment and prevention of human amyloid diseases. Here we demonstrated the use of graphene quantum dots (GQDs) as a potent inhibitor against the in vivo aggregation and toxicity of human islet amyloid polypeptide (IAPP), a hallmark of type 2 diabetes. GQDs initiated contact with IAPP through electrostatic and hydrophobic interactions as well as hydrogen bonding, which subsequently drove the peptide fibrillization off-pathway to eliminate the toxic intermediates. Such interactions, probed in vitro by a thioflavin T kinetic assay, fluorescence quenching, circular dichroism spectroscopy, a cell viability assay and in silico by discrete molecular dynamics simulations, translated to a significant recovery of embryonic zebrafish from the damage elicited by IAPP in vivo, as indicated by improved hatching as well as alleviated reactive oxygen species production, abnormality and mortality of the organism. This study points to the potential of using zero-dimensional nanomaterials for in vivo mitigation of a range of amyloidosis.

MeSH terms

  • Animals
  • Cell Survival / drug effects
  • Embryo, Nonmammalian / drug effects
  • Embryo, Nonmammalian / metabolism
  • Embryo, Nonmammalian / pathology
  • Graphite / chemistry*
  • Humans
  • Hydrogen Bonding
  • Hydrophobic and Hydrophilic Interactions
  • Insulin-Secreting Cells / cytology
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / metabolism
  • Islet Amyloid Polypeptide / chemistry*
  • Islet Amyloid Polypeptide / metabolism
  • Islet Amyloid Polypeptide / toxicity
  • Optical Imaging
  • Photoelectron Spectroscopy
  • Protein Structure, Secondary
  • Quantum Dots / chemistry*
  • Quantum Dots / toxicity
  • Reactive Oxygen Species / metabolism
  • Surface Properties
  • Zebrafish / growth & development

Substances

  • Islet Amyloid Polypeptide
  • Reactive Oxygen Species
  • Graphite