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

Treatment for Alzheimer's disease (AD), which currently focuses on inhibiting A β aggregation, fails to show effectiveness in people already presenting with symptoms of Alzheimer's disease. Strategies to synergexert neuroprotective effects and alleviate oxidative stress may be a promising approach to correct the pathological brain microenvironment. Based on the critical role of microglia in regulating the AD microenvironment, we describe here the development of Prussian blue / polyamide (PAMAM) dendrimer / Angiopep-2 (PPA) nanoparticles that regulate mitophagy in microglia as a potential AD therapy. PPA nanoparticles exhibit excellent blood-brain barrier (BBB) permeability and play a synergistic role in ROS clearance and restoring mitochondrial function in microglia. PPA nanoparticles effectively reduce neurotoxic A β aggregates and rescue cognitive function in the APP / PS1 model mice. Together, our data indicate that these multifunctional dendrimer nanoparticles exhibit effective neuroprotection and microglial modulation that can be promising as therapeutic approaches for AD.