Cu²⁺‐Chelatable and ROS‐Scavenging MXenzyme as NIR‐II‐Triggered Blood–Brain Barrier‐Crossing Nanocatalyst against Alzheimer's Disease

Abstract Transition‐metal dyshomeostasis has been identified as a critical pathogenic factor for the aggregates of amyloid‐beta (Aβ) peptide, which is associated with the onset and progression of Alzheimer's disease (AD). Excessive transition‐metal ions, especially copper ion (Cu²⁺), catalyze the formation of reactive oxygen species (ROS), triggering neuroinflammation and neuronal cell apoptosis. Therefore, developing a robust chelating agent can not only efficiently bind toxic Cu²⁺, but also simultaneously scavenge the over‐generated ROS that is urgently needed for AD treatment. In this work, a 2D niobium carbide (Nb₂C) MXene‐based nano‐chelator is constructed and its performance in suppressing Cu²⁺‐induced accumulation of aggregated Aβ peptide and acting as a nanozyme (MXenzyme) with powerful antioxidant property to scavenge excess cellular ROS is explored, and the intrinsic mechanism is revealed by computational simulation. Importantly, the benign photothermal effect of Nb₂C MXenzyme demonstrates the facilitated permeability of the blood–brain barrier under near‐infrared laser irradiation, conquering limitations of the most conventional anti‐AD therapeutic agents. This work not only demonstrates a favorable strategy for combating AD by engineering Nb₂C MXenzyme‐based neuroprotective nano‐chelator, but also paves a distinct insight for extending the biomedical applications of MXenes in treating transition‐metal dyshomeostasis‐and ROS‐mediated central nervous system diseases.