Cerium-doped carbon dots as dual-target agents against Alzheimer's β-amyloid fibrillogenesis and reactive oxygen species

Both fibrillogenesis of amyloid β-protein (Aβ) and elevated levels of reactive oxygen species (ROS) contribute to the pathogenesis of Alzheimer's disease (AD). Beyond Aβ aggregation inhibition, the complexity necessitates the development of comprehensive therapeutic interventions for halting AD progression. Herein, a dual-target agent capable of Aβ aggregation inhibition and ROS scavenging was synthesized by doping cerium into carbon dots (Ce CDs). Ce CDs with a high Ce (III)/Ce (IV) ratio of 0.67 can scavenge various ROS, including superoxide anion radicals, hydroxyl radicals, hydrogen peroxide, and Aβ 40 -induced ROS, thus mitigating cellular oxidative damage and rescuing cell viability. Additionally, Ce CDs present potent inhibition on Aβ 40 on-pathway fibrillization, disrupting the formation of highly ordered β-sheet structures and increasing cell viability from 50.2 % to 91.9 %. It is validated that the electrostatic interactions between Ce CDs and Aβ 40 are primarily responsible for preventing the conformational transition of Aβ 40 monomers. In vivo experiments with the transgenic Caenorhabditis elegans strain further validate the bifunctionality of Ce CDs in suppression of Aβ fibrillogenesis and attenuation of oxidative stress, thereby demonstrating the potential of combination therapy for AD. This finding highlights the important role of electrostatic interactions between Aβ and inhibitors in regulating Aβ aggregation, and provides new insights into the development of multifunctional agents for AD treatment.