A Functionalized Octahedral Palladium Nanozyme as a Radical Scavenger for Ameliorating Alzheimer's Disease

Oxidative stress is always mentioned as a pathologic appearance of Alzheimer's disease (AD). It is attributed to mitochondrial dysfunction closely linked to Aβ deposition and neurofibrillary tangles (NFTs). Octahedral palladium nanoparticles (Pd NPs) exhibited excellent antioxidant enzyme-like activity and outstanding biocompatibility, but the poor blood-brain barrier (BBB) permeability limits their application in the treatment of Alzheimer's disease. Herein, we constructed a borneol (Bor)-modified octahedral palladium (Pd@PEG@Bor) nanozyme platform to eliminate intracellular reactive oxygen species (ROS) and elevate epithelial cell penetrability. Based on in vitro and in vivo studies, we demonstrate that the Pd@PEG@Bor could efficiently reduce ROS and Ca²⁺ contents, maintain the mitochondrial membrane potential, and further protect the mitochondria in SH-SY5Y cells. Furthermore, the nanozymes could quickly accumulate in the brain of AD mice and alleviate pathological characteristics such as Aβ plaque deposition, neuron loss, and neuroinflammation. The learning ability and memory function of AD mice are also significantly improved. Overall, this work indicates that the Pd@PEG@Bor nanozymes could delay the progression of AD by regulating ROS levels and also provides a new strategy for the treatment of AD.