Light-Induced Chiral Iron Copper Selenide Nanoparticles Prevent β-Amyloidopathy In Vivo

The accumulation and deposition of β-amyloid (Aβ) plaques in the brain is considered a potential pathogenic mechanism underlying Alzheimer's disease (AD). Chiral l/d-Fe_x Cu_y Se nanoparticles (NPs) were fabricated that interfer with the self-assembly of Aβ42 monomers and trigger the Aβ42 fibrils in dense structures to become looser monomers under 808 nm near-infrared (NIR) illumination. d-Fe_x Cu_y Se NPs have a much higher affinity for Aβ42 fibrils than l-Fe_x Cu_y Se NPs and chiral Cu_2-x Se NPs. The chiral Fe_x Cu_y Se NPs also generate more reactive oxygen species (ROS) than chiral Cu_2-x Se NPs under NIR-light irradiation. In living MN9D cells, d-NPs attenuate the adhesion of Aβ42 to membranes and neuron loss after NIR treatment within 10 min without the photothermal effect. In-vivo experiments showed that d-Fe_x Cu_y Se NPs provide an efficient protection against neuronal damage induced by the deposition of Aβ42 and alleviate symptoms in a mouse model of AD, leading to the recovery of cognitive competence.