Sulfur‐Mediated Hollow Engineering FeSe 2 /CuCoSe 2 Heterojunction Nanozyme for Synergistic NIR‐II Photothermal/Enzymatic Therapy

The facile construction of high‐performance photothermal nanozymes that simultaneously possess hollow architectures and heterojunction structures is highly appealing for tumor therapy. Herein, sulfur‐mediated hollow engineering was used to fabricate S‐FeSe 2 /CuCoSe 2 heterojunction nanozymes via one‐step hydrothermal synthesis, with uniform ∼ 200 nm hollow cubic morphology and homogeneous elemental distribution. S‐doping and the hollow heterojunction structure of S‐FeSe 2 /CuCoSe 2 endow the nanozyme with excellent photothermal conversion efficiency (PCE) at NIR‐II regime (1064 nm), which reaches as high as 56.1%, in contrast to 33.7% for pristine FeSe 2 /CuCoSe 2 . S‐FeSe 2 /CuCoSe 2 nanozymes also show better performance in peroxidase (POD)‐like activity ( K m = 0.28 mM, V max = 43.8 nM/s) than FeSe 2 /CuCoSe 2 ( K m = 0.54 mM, V max = 27.3 nM/s). Meanwhile, its oxidase (OXD)‐ and glutathione peroxidase (GPx)‐like activities are significantly enhanced. In vitro, S‐FeSe 2 /CuCoSe 2 showed low cytotoxicity to normal cells and induced 75.4% apoptosis of 4T1 cells under laser irradiation via ROS burst and mitochondrial damage. In vivo 4T1 tumor models confirmed efficient synergistic photothermal/enzymatic therapy with significant tumor inhibition and bare toxicity. This work offers a novel strategy for designing high‐performance heterojunction nanozymes for cancer therapy.