Ruthenium Dioxide Nanoparticles Treat Alzheimer’s Disease by Inhibiting Oxidative Stress and Alleviating Neuroinflammation

Oxidative stress and neuroinflammation have received widespread attention as mechanisms of Alzheimer's disease (AD) pathogenesis. Oxidative stress, serving as a "bridge" between various hypotheses, has been shown to interact with several pathological features (neuroinflammation, β-amyloid deposition) and forms a vicious circle that accelerates the progression of AD. Herein, we report ruthenium dioxide nanoparticles (RuO2 NPs) with diverse enzymatic activities and reactive oxygen species (ROS) elimination functions. The poly(vinylpyrrolidone) (PVP) on the surface of RuO2 NPs was used to link with borneol (Bor) to help it pass through the blood–brain barrier (BBB). In vitro and in vivo experiment results have shown that RuO2@Bor possesses good biocompatibility and multiple antioxidant-like enzymatic activities, which can scavenge ROS, protect neurons from oxidative damage, and repair impaired mitochondrial function. In addition, RuO2@Bor could also regulate microglia polarization (from pro-inflammatory M1-phenotype microglial to anti-inflammatory M2 phenotype microglial) and inhibit the release of pro-inflammatory factors (TNF-α, IL-6) to effectively relieve neuroinflammation. In vivo experiments further demonstrated that RuO2@Bor not only effectively improved the cognitive and memory abilities of AD model mice but also acted as an effective neuroprotective agent. The results suggest that RuO2@Bor would be a potential drug for the multitarget treatment of AD.