Biofilm-modified Prussian blue improves memory function in late-stage Alzheimer's disease mice with triple therapy

Alzheimer's disease (AD) is a neurodegenerative disease that is significantly characterized by cognitive and memory impairments, which worsen significantly with age. In the late stages of AD, metal ion disorders and an imbalance of reactive oxygen species (ROS) levels occur in the brain microenvironment, which causes abnormal aggregation of β-amyloid (Aβ), leading to a significant worsening of the AD symptoms. Therefore, we designed a composite nanomaterial of macrophage membranes-encapsulated Prussian blue nanoparticles (PB NPs/MM). Prussian blue nanoparticles (PB NPs) are capable of chelating Cu²⁺ and reducing ROS. Macrophage membranes (MM) have advantages over liposomal and erythrocyte membrane carriers, including inflammatory targeting capabilities and more effective immune evasion. Concurrently, the excellent photothermal ability of PB NPs can briefly open the blood-brain barrier (BBB) under near-infrared laser irradiation, which improves the transport efficiency of PB NPs/MM across the BBB and ablates Aβ deposition, thus achieving optimal therapeutic efficacy. In vitro experiments demonstrated that PB NPs/MM is a multifunctional nanosystem, which can effectively inhibit Cu²⁺-induced Aβ monomers aggregation, photothermally depolymerize Aβ fibrils, and attenuate oxidative stress through the combined treatment of chelating metals, photothermal therapy and scavenging ROS. In behavioral experiments, it also significantly improved the cognitive and learning deficits in late-stage APP/PS1 mice, thereby providing new ideas for the treatment of late-stage AD and other neurodegenerative diseases.