Cerium-Rutin Coordination Polymer Nanoparticles for Scavenging ROS and Inhibiting Amyloid-β Fibrillation in Alzheimer's Disease.

The abnormal accumulation of amyloid-beta (Aβ) triggers cellular dysfunction and tissue damage through processes including reactive oxygen species (ROS) and neuroinflammation, ultimately leading to the manifestation of AD symptoms. However, existing studies have revealed that the isolated clearance of amyloid-beta (Aβ), reactive oxygen species (ROS), or neuroinflammation confers no significant benefit on cognitive and memory function in AD patients. Thus, given the complex pathogenic mechanisms underlying AD, multitarget synergistic therapy represents a promising therapeutic strategy. Herein, we reported coordination polymer nanoparticles, Ce-Ru@Trf NPs, composed of cerium (Ce), rutin (Ru), and transferrin (Trf), which efficiently scavenge various ROS and anti-neuroinflammation and inhibit Aβ fibrillization. Owing to Trf modification, its accumulation in brain tissues increased significantly. The Ce-Ru@Trf NPs also dampened neuroinflammation by redirecting microglia toward the M2 phenotype and curtailing proinflammatory factor release. In an AD APP/PS1 model, it significantly achieved a neuroprotective effect and improved cognitive function. The findings suggest that biocompatible coordination polymers composed of metals and natural products may offer a viable therapeutic strategy for Alzheimer's disease.