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

• Published in: Small (Weinheim an der Bergstrasse, Germany) Germany), 2022-09, Vol.18 (39), p.n/a
• Main Authors: Du, Chengjuan, Feng, Wei, Dai, Xinyue, Wang, Jianhong, Geng, Daoying, Li, Xiaodan, Chen, Yu, Zhang, Jun
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Apoptosis; Biocompatibility; Biomedical materials; Blood-brain barrier; Central nervous system; Chelating agents; Chelation; Chemical compounds; Copper; copper ions chelating therapy; Infrared lasers; MXenzymes; Nanotechnology; nanozymes; Nb 2C MXenes; Niobium carbide; Peptides; Pharmacology; reactive oxygen species scavenging; Scavenging
• ISSN: 1613-6810; 1613-6829
• DOI: 10.1002/smll.202203031

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. An integrated nano‐chelator with cascade nanozyme based on 2D niobium carbide (Nb2C) MXene is developed to selectively capture Cu2+ and eliminate excessive reactive oxygen species against neurodegenerative diseases. This work demonstrates that Nb2C MXenzyme features the desirable clinical translation potential, largely based on the facile formulation, antioxidant enzyme‐mimicking performance, and effective blood‐brain barrier penetration under near infrared laser stimulus.