Cu<sup>2+</sup>‐Chelatable and ROS‐Scavenging MXenzyme as NIR‐II‐Triggered Blood–Brain Barrier‐Crossing Nanocatalyst against Alzheimer's Disease
Chengjuan Du, Wei Feng, Xinyue Dai, Jianhong Wang, Daoying Geng, Xiaodan Li, Yu Chen, Jun Zhang
Abstract
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 (Cu 2+ ), 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 Cu 2+ , but also simultaneously scavenge the over‐generated ROS that is urgently needed for AD treatment. In this work, a 2D niobium carbide (Nb 2 C) MXene‐based nano‐chelator is constructed and its performance in suppressing Cu 2+ ‐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 Nb 2 C 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 Nb 2 C 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.