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

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.