A Ru3+-Functionalized-NMOF Nanozyme as an Inhibitor and Disaggregater for β-Amyloid Aggregates

Alzheimer’s Disease (AD) heavily impacts human lives, and is becoming serious with the aging society. Inhibiting and disaggregating β-amyloid aggregates is a possible solution for AD therapy. In this study, a novel type of nanozymes based on Ru3+ chelated nanoscale metal organic frameworks (Ru3+-NMOFs), displaying strong peroxidase-like activity, was proposed as an inhibitor and disaggregater for β-amyloid aggregates. As a high concentration of hydrogen peroxide was present at the sites of β-amyloid aggregates, Ru3+-NMOFs could catalyze hydrogen peroxide to hydroxyl radicals. Thus, hydroxyl radical would attack the β-amyloid chain for oxidation, enhancing its hydrophilicity, and resulting in a decreased hydrophobic interaction and reduced aggregation degree. Ru3+-NMOFs behaved effective in inhibiting as well as disaggregating β-amyloid fibrils both in vitro and in vivo. Additionally, the reduction of β-amyloid aggregates and the attenuation of reactive oxygen species transfer led to lower levels of inflammatory factors, which would be beneficial in alleviating AD symptom. In a typical application, Ru3+-NMOFs could mitigate the paralysis of C. elegans CL2120 and increase survival rates. This study opens a new avenue for MOFs based nanozymes as a potential treatment agent for AD therapy.