A Ru3+-functionalized-NMOF nanozyme as an inhibitor and disaggregator of β-amyloid aggregates

J Mater Chem B. 2024 Dec 4;12(47):12239-12250. doi: 10.1039/d4tb01313a.

Abstract

Alzheimer's disease (AD) heavily impacts human lives and is becoming serious as societies age. Inhibiting and disaggregating β-amyloid aggregates is a possible solution for AD therapy. In this study, a novel type of nanozyme based on Ru3+-chelated nanoscale metal organic frameworks (Ru3+-NMOFs), displaying strong peroxidase-like activity, was proposed as an inhibitor and disaggregator of β-amyloid aggregates. As a high concentration of hydrogen peroxide is present at the sites of β-amyloid aggregates, Ru3+-NMOFs could catalyze the conversion of hydrogen peroxide to hydroxyl radicals. Thus, these hydroxyl radicals would attack the β-amyloid chain, oxidizing it to enhance its hydrophilicity, which results in a decreased hydrophobic interaction and reduced degree of aggregation. Ru3+-NMOFs could effectively inhibit as well as disaggregate β-amyloid fibrils both in vitro and in vivo. Additionally, the reduction of the β-amyloid aggregates and the attenuation of reactive oxygen species transfer led to lower levels of inflammatory factors, which could be beneficial in alleviating AD symptoms. In a typical treatment, Ru3+-NMOFs could mitigate the paralysis of C. elegans CL2120 and elevate survival rates. This study opens a new avenue for MOF-based nanozymes as potential treatment agents for AD therapy.

MeSH terms

  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / metabolism
  • Amyloid beta-Peptides* / antagonists & inhibitors
  • Amyloid beta-Peptides* / metabolism
  • Animals
  • Caenorhabditis elegans / drug effects
  • Caenorhabditis elegans / metabolism
  • Humans
  • Metal-Organic Frameworks / chemistry
  • Metal-Organic Frameworks / pharmacology
  • Particle Size
  • Protein Aggregates* / drug effects
  • Reactive Oxygen Species / metabolism
  • Ruthenium* / chemistry
  • Ruthenium* / pharmacology

Substances

  • Amyloid beta-Peptides
  • Protein Aggregates
  • Ruthenium
  • Metal-Organic Frameworks
  • Reactive Oxygen Species