Amino Acid Functionalized Superparamagnetic Nanoparticles Inhibit Lysozyme Amyloid Fibrillization

Chemistry. 2019 Jun 4;25(31):7501-7514. doi: 10.1002/chem.201806262. Epub 2019 May 9.

Abstract

Nanoparticles have great potential to be used in various biomedical applications, including therapy or diagnosis of amyloid-related diseases. The physical and chemical properties of iron oxide superparamagnetic nanoparticles (MNPs) functionalized with different amino acids (AAs), namely, with lysine (Lys), glycine (Gly), or tryptophan (Trp), have been characterized. The cytotoxicity of nanoparticles and their effect on amyloid fibrillization of lysozymes in vitro was also verified. The AA-MNPs under study are nontoxic to human SHSY5Y neuroblastoma cells. Moreover, the AA-MNPs were able to significantly inhibit lysozyme amyloid fibrillization and destroy amyloid fibrils. Kinetic studies revealed that the presence of AA-MNPs affected lysozyme fibrillization, namely, the lag phase and steady-state phase of the growth curves. The most effective activities were observed for Trp-MNPs, which revealed the importance of aromatic rings in the structure of AAs used as coating agents. The obtained results indicate the possible application of these AA-MNPs in the treatment of amyloid diseases associated with lysozyme or other amyloidogenic proteins.

Keywords: aggregation; amino acids; amyloid beta-peptides; magnetic properties; nanoparticles.

MeSH terms

  • Amino Acids / chemistry*
  • Amino Acids / pharmacology*
  • Amyloid / antagonists & inhibitors*
  • Amyloid / chemistry*
  • Amyloid / ultrastructure
  • Animals
  • Cell Line, Tumor
  • Chickens
  • Humans
  • Kinetics
  • Magnetite Nanoparticles / chemistry*
  • Magnetite Nanoparticles / ultrastructure
  • Models, Molecular
  • Muramidase / chemistry*
  • Muramidase / ultrastructure
  • Protein Aggregates / drug effects*
  • Protein Conformation / drug effects

Substances

  • Amino Acids
  • Amyloid
  • Magnetite Nanoparticles
  • Protein Aggregates
  • Muramidase