A cascaded enzyme system based on the catalase-like activity of Ti3C2Tx 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 Ti 3 C 2 T x MXene , a kind of two-dimensional (2D) material with photothermal capability. Ti 3 C 2 T x 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 Ti 3 C 2 T x -GOx/DOX-PEG, for anticancer purposes. Ti 3 C 2 T x -GOx/DOX-PEG exhibited a photothermal conversion efficiency of ∼28.7% at 808 nm, enabling its use for near-infrared light-based photothermal therapy (PTT). In addition, Ti 3 C 2 T x could decompose H 2 O 2 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 H 2 O 2 for the production of O 2 by Ti 3 C 2 T x . 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 Ti 3 C 2 T x as well as various enzymatic reactions catalyzed by Ti 3 C 2 T x -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 Ti 3 C 2 T x -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.