Neuroprotective Nanoscavenger Induces Coaggregation of β-Amyloid and Facilitates Its Clearance in Alzheimer's Disease Brain

The accumulation of soluble beta-amyloid aggregates (sA beta s) is one of the main culprits in Alzheimer's disease (AD) progression, which can lead to synaptic dysfunction and subsequent neurodegeneration. Herein, we describe a nanoscavenger with novel structure that can cross the blood-brain barrier (BBB), accurately collect neurotoxic sA beta s, and facilitate amounts of beta-amyloid (A beta) clearance. The nanoscavenger is composed of an A beta-binding albumin nanoparticle surface-decorated with Immunoglobulin G (IgG) and brain-targeting peptide (PEGylated B6). During transport across the BBB, the nanoscavenger detaches PEGylated B6 and enters the brain. Then, the nanoscavenger competitively inhibits the formation of neurotoxic sA beta s, and induces the coaggregation of preexistent sA beta s, leading to the formation of nanoscavenger/A beta coaggregates. Such aggregates are readily cleared by microglia via antibody-dependent cell-mediated phagocytosis (ADCP) even under an inflammatory environment in APP/PS1 mice. Our nanoscavenger demonstrates a strategy to design a synthetic nanostructure to modulate disease-related biological processes, providing a new approach in nanomedicine development. [GRAPHICS] .