Silica Nanodepletors: Targeting and Clearing Alzheimer's beta-Amyloid Plaques

Abstract

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