Cu2+‐Chelatable and ROS‐Scavenging MXenzyme as NIR‐II‐Triggered Blood–Brain Barrier‐Crossing Nanocatalyst against Alzheimer's Disease. Issue 39 (25th August 2022)

• Record Type: Journal Article
• Authors: Du, Chengjuan; Feng, Wei; Dai, Xinyue; Wang, Jianhong; Geng, Daoying; Li, Xiaodan; Chen, Yu; Zhang, Jun
• Is Part Of: Small. Volume 18:Issue 39(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-08-25
• Subjects: Alzheimer's disease -- copper ions chelating therapy -- MXenzymes -- nanozymes -- Nb 2C MXenes -- reactive oxygen species scavenging; Nanotechnology -- Periodicals; Nanoparticles -- Periodicals; Microtechnology -- Periodicals; 620.5
• DOI: 10.1002/smll.202203031
• Languages: English
• ISSNs: 1613-6810

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 (Nb2 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 Nb2 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 Nb2 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. Abstract : An integrated nano‐chelator with cascade nanozyme based on 2D niobium carbide (Nb2 C) MXene is developed to selectively capture Cu 2+ and eliminate excessive reactive oxygen species against neurodegenerative diseases. This work demonstrates that Nb2 C 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.