A Neutrophil Membrane-Encapsulated Pd/hCeO2 Nanoformulation for Alleviating Age-Dependent Perioperative Neurocognitive Disorders.

Perioperative neurocognitive disorders (PND) are a prevalent and disabling complication in elderly patients after anesthesia and surgery, imposing a growing clinical burden in aging societies. Despite its high incidence, effective therapies for PND remain unavailable. Surgery-induced neuroinflammation, characterized by excessive oxidative stress, microglial activation, and blood-brain barrier (BBB) disruption, plays a central role in the development of PND. Here, we develop a PCN biomimetic nanozyme platform based on homologous, highly adhesive neutrophil membrane-encapsulated Pd/hCeO2 nanoparticles for the treatment of age-related PND. Benefiting from the innate inflammation-targeting properties of neutrophil membranes, PCN efficiently traverses the compromised BBB and precisely accumulates in neuroinflammatory regions. PCN exhibits potent reactive oxygen species scavenging activity and markedly attenuates neuroinflammation in the aging brain, while preserving BBB integrity. Specifically, PCN suppresses the pro-inflammatory and dysmetabolic state of microglia through inhibition of the glycolytic pathway and promotion of aerobic respiration, thereby protecting synaptic function and improving cognitive performance in aged PND mice. In general, this study identifies a biomimetic nanozyme strategy as a promising therapeutic approach for mitigating postoperative cognitive decline or other inflammatory damage in the aging brain.