Polyoxometalate-based nanozyme: Design of a multifunctional enzyme for multi-faceted treatment of Alzheimer’s disease

Proteolytic degradation of amyloid-β (Aβ) aggregates and clearance of Aβ-induced reactive oxygen species (ROS) have received significant attention for the treatment of Alzheimer’s disease (AD). However, it is difficult, and often unfeasible, to directly upregulate or transport intracellular native enzymes. More importantly, penetration of the blood-brain barrier (BBB) has presented a major impediment. Herein, we report on the rational design of a polyoxometalatebased nanozyme with both protease-like activity for depleting Aβ aggregates, and superoxide dismutase (SOD)-like activity for scavenging Aβ-mediated ROS. Furthermore, this nanozyme acts as a metal chelator to remove Cu from Cu-induced Aβ oligomers. More intriguingly, the nanozyme can cross the BBB and exhibits low toxicity. This work provides new insights into the design and synthesis of inorganic nanozymes as multifunctional therapeutic agents in the treatment of AD.