A Dual-Responsive Claringbullite-Like Nanozyme for Inhibition of Non-Small Cell Lung Cancer Progression

A Claringbullite-like nanozyme CuCl_0.38F0.1(OH)_1.51•nH₂O (denoted as FCN) was fabricated by a simple "one-pot" method for non-small cell lung cancer (NSCLC) treatment. Acting as an "AND" logic gate, the pH/GSH dual-responsive property allowed FCN to selectively target tumor cells while minimizing side effects. FCN exhibited the glutathione catalase (CAT)-like, peroxidase (POD)-like, and peroxidase (GPx)-like activities. The enhanced catalytic activity of FCN was attributed to its improved charge transfer capability, as evidenced by its performance in H₂O₂ decomposition. FCN prompted cuproptosis and ferroptosis by depriving glutathione (GSH), elevating ROS, alleviating hypoxia, and inhibiting glycolysis in A549 cells. Moreover, FCN elicited the active anti-tumor immune responses, including the macrophage phenotype transition, the elevated levels of CD8⁺ T cells, and the decreased levels of regulatory T (Treg) cells, thereby enhancing therapeutic efficacy against NSCLC. Furthermore, FCN treatment significantly attenuated lung metastasis in mice bearing Lewis lung carcinoma (LLC) cells. This work opens up a new avenue for the development of metal-halide nanozymes for tumor catalytic therapy.