Blood-brain barrier Permeable nanoparticles for Alzheimer's disease treatment by selective mitophagy of microglia

Current treatments for Alzheimer's disease (AD) that focus on inhibition of A beta aggregation failed to show effectiveness in people who already had Alzheimer's symptoms. Strategies that synergistically exert neuro-protection and alleviation of oxidative stress could be a promising approach to correct the pathological brain microenvironment. Based on the key roles of microglia in modulation of AD microenvironment, we describe here the development of Prussian blue/polyamidoamine (PAMAM) dendrimer/Angiopep-2 (PPA) nanoparticles that can regulate the mitophagy of microglia as a potential AD treatment. PPA nanoparticles exhibit superior blood -brain barrier (BBB) permeability and exert synergistic effects of ROS scavenging and restoration of mitochondrial function of microglia. PPA nanoparticles effectively reduce neurotoxic A beta aggregate and rescue the cognitive functions in APP/PS1 model mice. Together, our data suggest that these multifunctional dendrimer nanoparticles exhibit efficient neuroprotection and microglia modulation and can be exploited as a promising approach for the treatment of AD.

Automated summary

In this study, the authors developed Prussian blue/polyamidoamine (PAMAM) dendrimer/Angiopep-2 (PPA) nanoparticles for the treatment of Alzheimer's disease (AD). These nanoparticles exhibited superior blood-brain barrier permeability and had synergistic effects on scavenging ROS and restoring mitochondrial function of microglia. The nanoparticles effectively reduced neurotoxic A beta aggregate and improved cognitive functions in the AD mouse model.