A cascaded enzyme system based on the catalase-like activity of Ti₃C₂T_x MXene nanosheets for the efficient combination cancer therapy

Catalytic therapy with enzymes and nanozymes is a promising approach to cancer treatment. However, it often proves inadequate when used as a standalone treatment. This work presents the catalase (CAT)-like activity of Ti3C2Tx MXene, a kind of two-dimensional (2D) material with photothermal capability. Ti3C2Tx nanosheets were then used to load glucose oxidase (GOx) and the anticancer drug doxorubicin hydrochloride (DOX), and modified with polyethylene glycol (PEG) to obtain an enzyme cascade system, named Ti3C2Tx-GOx/DOX-PEG, for anticancer purposes. Ti3C2Tx-GO(x)/DOX-PEG exhibited a photothermal conversion efficiency of similar to 28.7% at 808 nm, enabling its use for near-infrared light-based photothermal therapy (PTT). In addition, Ti3C2Tx could decompose H2O2 to O-2 in cancer cells, thereby enhancing starvation therapy by sensitizing GOx. Furthermore, alleviation of hypoxia could sensitize the chemotherapy of DOX. The decomposition of glucose by GOx could also generate H2O2 for the production of O-2 by Ti(3)C(2)Tx. Ultimately, the cycling of the enzyme cascade reaction could alleviate tumor hypoxia and enable enhanced chemo/starvation/photothermal combination therapy. The CAT-like behavior of Ti3C2Tx as well as various enzymatic reactions catalyzed by Ti3C2Tx-GOx/DOX-PEG were systematically investigated by intra- and extracellular experiments. Results from both in vitro and in vivo studies demonstrated the effective anticancer capability of Ti3C2Tx-GOx/DOX-PEG. This enzyme cascade system has the potential to enhance material utilization and reduce side effects, thus opening up new opportunities for designing efficient and safe anticancer systems.