Transition Metal Oxide-Decorated MXenes as Drugless Nanoarchitectonics for Enriched Nanocatalytic Chemodynamic Treatment

Despite their unique characteristics, the recently emerged two-dimensional (2D) MXenes with sole photothermal conversion ability are required to explore their superfluous abilities in biomedicine. To this end, small-molecule-based chemotherapeutics suffer from various shortcomings of time-consuming and expensiveness in terms of molecular docking and subsequent mechanistic (preclinical/clinical) performance checks, hampering their full potential of precisely eradicating diseases. This study demonstrates the fabrication of Ti 3 C 2 MXene nanosheets (TC-MX NSs) and decoration with transition metal oxides, i.e., copper oxide (Cu 2 O/MX, shortly denoted as CO-MX NCs) as drugless nanoarchitectonics for synergistic photothermal (PTT)-chemodynamic therapeutic (CDT) efficacies. Initially, the monolayer/few-layered TC-MX NSs are prepared using the chemical etching-assisted ultrasonic exfoliation method and then deposited with Cu 2 O nanoconstructs using the in situ reduction method. Further, the photothermal ablation under near-infrared (NIR)-II laser irradiation evidently showed mild PTT effects of CO-MX NCs. The deposited Cu 2 O on TC-MX NSs facilitated the release of copper (Cu + ) ions in the acidic microenvironment intracellularly for Fenton-like reaction-assisted CDT effects and enriched PTT effects synergistically. Mechanistically, these deadly free radicals intracellularly imbalanced the glutathione (GSH) levels and subsequently resulted in mitochondrial dysfunction, inducing apoptosis of 4T1 cells. Finally, the in vivo investigations in BALB/c mice confirmed the substantial therapeutic effects of ablating breast carcinoma. Together, these findings demonstrated the potential synergistic photothermal-chemodynamic therapeutic effects of the designed CO-MX NCs as drugless nanoarchitectonics against breast carcinoma. This article is protected by copyright. All rights reserved