Therapeutic nanosweepers promote β-amyloid removal from the brain for Alzheimer's disease treatment

Abstract

Formation of neurotoxic β-amyloid (Aβ) deposits is generally believed to be a crucial pathogenic event in Alzheimer's disease (AD). However, current Aβ-targeting medicines show limited therapeutic efficacy due to ineffective Aβ removal and limited blood–brain barrier (BBB) penetration capability. Herein, a therapeutic nanosweeper (NS) with Aβ removal capability is developed. NS can be efficiently loaded into neutrophils (NE) to form NS/NE to improve its BBB crossing efficiency and preserve its Aβ removal capability after being released from neutrophils. With this capability, NS can be efficiently delivered into the brain in the form of NS/NE owing to its chemotaxis to inflammatory factors released from AD brain. Moreover, NS released from NS/NE preserved its Aβ removal capability, thereby significantly alleviating the pathological symptoms of Aβ deposition and neuronal apoptosis in AD mice. This work demonstrated the potential of NS in the development of novel and effective AD therapies.