Rationally Designed CeNP@MnMoS4 Core‐Shell Nanoparticles for Modulating Multiple Facets of Alzheimer's Disease

Abstract Alzheimer's disease (AD) is a complicated multifactorial syndrome. Lessons have been learned through failed clinical trials that targeting multiple key pathways of the AD pathogenesis is necessary to halt the disease progression. Here, we construct core‐shell nanoparticles (CeNP@MnMoS 4 ) targeting multiple key pathways of the AD pathogenesis, including elimination of toxic metal ions, decrease of oxidative stress, and promotion of neurite outgrowth. The SOD activity and copper removal capacity of CeNP@MnMoS 4 ‐ n ( n represents the number of layers of MnMoS 4 , n =1–5) was investigated in vitro. We found that CeNP@MnMoS 4 ‐3 made an excellent balance between SOD activity and copper removal capacity. The effect of CeNP@MnMoS 4 ‐3 on Cu 2+ ‐induced Aβ aggregation was studied by gel electrophoresis, transmission electron microscope (TEM), and atomic force microscopy (AFM). Compared with MnMoS 4 or CeNP alone, a synergistic effect was observed. Moreover, CeNP@MnMoS 4 ‐3 promoted neurite outgrowth in a dose‐dependent manner. Taken together, the results reported in this work show the potential of new multifunctional core‐shell nanoparticles as AD therapeutics.