Ultrathin CuFe₂S₃ nanosheets derived from CuFe-layered double hydroxide as an efficient nanoagent for synergistic chemodynamic and NIR-II photothermal therapy

Ultrathin two-dimensional (2D) nanosheets (NSs) have been widely explored as nanoagents for multimodal cancer therapies, such as photothermal therapy (PTT) combined with chemodynamic therapy (CDT). However, it is still a challenge to prepare 2D NSs with good performance in both CDT and NIR-II PTT. Here, we report the preparation of ultrathin 2D CuFe₂S₃ NSs as an efficient nanoagent for synergistic CDT and NIR-II PTT to ablate cancer cells/tumors. Ultrathin 2D CuFe₂S₃ NSs are first prepared by sulfurization of ultrathin CuFe-LDH NSs via a simple hydrothermal treatment. After modification with polyethylene glycol (PEG), the PEG-modified CuFe₂S₃ NSs (CuFe₂S₃-PEG) show broadband NIR-II absorption and excellent photothermal conversion efficiency (~55.86%) at 1064 nm. Moreover, the overproduced glutathione in the tumor microenvironment can react with CuFe₂S₃-PEG NSs to release Fe²⁺ and Cu⁺, thus activating Fenton reaction to efficiently produce hydroxyl radicals (·OH). Importantly, the photothermal effect of CuFe₂S₃-PEG could further synergistically improve the Fenton reaction by increasing the local temperature. In vitro and in vivo results reveal that the CuFe₂S₃-PEG has remarkable synergistic CDT/PTT antitumor activity. This study has proven that the metal chalcogenide NSs of CuFe₂S₃-PEG can be used as an efficient nanoagent for multimodal cancer therapies, which could also be promising in other applications like biosensors, drug delivery and antibacterial.