3-Bromopyruvate-Loaded Ti 3 C 2 MXene/Cu 2 O Nanosheets for Photoacoustic Imaging-Guided and Hypoxia-Relieving Enhanced Photothermal/Chemodynamic Therapy.

Chemodynamic therapy (CDT) is an innovative and effective treatment that relies on the Fenton or Fenton-like reaction, in which endogenous H 2 O 2 overproduction is converted into cytotoxic hydroxyl radicals ( • OH) to suppress tumor growth. Nevertheless, the therapeutic efficiency of CDT is severely restricted by undesirable properties, such as reaction conditions and catalyst performance. Herein, a 2D Ti 3 C 2 MXene/Cu 2 O nanosheet (MCP NS)-based multifunctional nanoplatform (3-BP@MCG NSs) has been constructed, in which glucose oxidase (GOx) and respiration inhibitor 3-bromopyruvate (3-BP) are sequentially embedded. In this structure, the copper-based catalyst Cu 2 O releases Cu + in an acid-triggered manner in the tumor microenvironment (TME), which activates the Fenton-like reaction to catalyze the generation of • OH for CDT. The composite has excellent photothermal properties and a high-resolution photoacoustic imaging (PAI) capability in the near-infrared (NIR) region, and especially under NIR irradiation, the photothermal effect generated by the nanosheets accelerates catalysis. GOx is a natural enzyme catalyst for depleting glucose and oxygen content in cells, upregulating H 2 O 2 levels in situ , and thereby improving the therapeutic effect of CDT. What is more, the supported 3-BP not only reduces oxygen consumption to alleviate hypoxia levels but also inhibits the glycolysis process and lowers ATP levels by suppressing hexokinase activity. As a result, 3-BP@MCG NSs optimize the unique properties of MCP NSs, GOx, and 3-BP via mutual promotion, realizing self-enhanced PTT/CDT synergistic therapy. This work establishes an emerging strategy for highly efficient PAI-guided integrated treatment and provides a proof of concept for the cooperation of hypoxia relief and in situ H 2 O 2 and NIR synergistic enhancement to improve therapeutic efficiency.