Silica Nanodepletors: Targeting and Clearing Alzheimer's β‐Amyloid Plaques

Abstract

Abnormal accumulation of β-amyloid (Aβ) peptide aggregates in the brain is a major hallmark of Alzheimer's disease (AD). Aβ aggregates interfere with neuronal communications, ultimately causing neuronal damage and brain atrophy. Much effort has been made to develop AD treatments that suppress Aβ aggregate formation, thereby attenuating Aβ-induced neurotoxicity. Here, the design of Aβ nanodepletors consisting of ultralarge mesoporous silica nanostructures and anti-Aβ single-chain variable fragments, with the goal of targeting and eliminating aggregative Aβ monomers, is reported. The Aβ nanodepletors impart a notable decline in Aβ aggregate formation, resulting in significant mitigation of Aβ-induced neurotoxicity in vitro. Furthermore, stereotaxic injections of Aβ nanodepletors into the brain of an AD mouse model system successfully suppress Aβ plaque formation in vivo up to ≈30%, suggesting that Aβ nanodepletors can serve as a promising antiamylodoisis material.