Sulfur-Mediated Hollow Engineering FeSe2/CuCoSe2 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-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 (Km = 0.28 mM, Vmax = 43.8 nM/s) than FeSe2/CuCoSe2 (Km = 0.54 mM, Vmax = 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.