Copper decorated Ti₃C₂ nanosystem with NIR-II-induced GSH-depletion and reactive oxygen species generation for efficient nanodynamic therapy

Abstract Nanodynamic therapy (NDT) based on reactive oxygen species (ROS) production has been envisioned as an effective cancer treatment. However, the efficacy is limited by hypoxia, insufficient hydrogen peroxide conversion, and high glutathione (GSH) levels in tumor microenvironment (TME). To solve these issues, we proposed designed a biocompatible, resistant Cu-modified Ti 3 C 2 nanocomposite (Ti -Cu-PEG), which can efficiently deplete endogenous GSH cells, smartly respond to NIR-II light irradiation with in-depth tissue penetration achieve photothermally enhanced photodynamic (PDT) catalytic therapy. Specifically, -Cu-PEG reacted produce singlet ( 1 O ) under irradiation, catalyzed highly expressed H generate ·OH. In addition, significantly decreased intracellular GSH, reduced chances of reaction between ROS thus promoting effect. Moreover, intrinsically photothermal conversion efficiency further promotes NDT process. vitro vivo experiments, nanosystem showed excellent antitumor effect 4T1 tumor-bearing mice amplifying oxidative stress stimulation. This work highlights easily synergistic remodeling TME combined enhance therapeutic