Sulfur-Mediated Hollow Engineering FeSe₂/CuCoSe₂ Heterojunction Nanozyme for Synergistic NIR-II...

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-FeSe₂/CuCoSe₂ 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-FeSe₂/CuCoSe₂ 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 FeSe₂/CuCoSe₂. S-FeSe₂/CuCoSe₂ nanozymes also show better performance in peroxidase (POD)-like activity (K_m = 0.28 mM, V_max = 43.8 nM/s) than FeSe₂/CuCoSe₂ (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-FeSe₂/CuCoSe₂ 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.