Boosting Enzyme-like\nActivities <i>via</i> Atomization of Cerium for Tumor Microenvironment-Responsive\nCascade\nTherapy

Nanozyme catalytic therapeutic efficacy is limited by\nthe finite\nenzyme activity and specificity. In this work, nitrogen-doped carbon\nloaded with a cerium single-atom nanozyme (Ce SAs@NC) is synthesized,\nexhibiting tumor specificity and excellent multiple enzyme-like activities.\nCompared with nitrogen-doped carbon loaded with CeO<sub>2</sub> nanoparticles,\nCe SAs@NC shows excellent peroxidase-like and catalase-like activity.\nCe SAs@NC can convert intracellular hydrogen peroxide into cytotoxic\nhydroxyl radical and O<sub>2</sub>, which can be further transferred\nto superoxide radicals. Cascade enzyme reactions not only alleviate\nthe hypoxic microenvironment of tumors but also induce lipid peroxidation\nand apoptosis or necrosis of tumor cells. The mild photothermal action\nwill enhance the enzyme-like activities of Ce SAs@NC rather than induce\nthe production of heat shock proteins to protect tumor cells. In addition,\nCe SAs@NC can regulate the immune environment, stimulate M1 macrophages\nto trigger immune responses, and inhibit tumor proliferation. Thanks\nto the combination of the size effect of the single atoms, photothermal\ninfluence, multiple enzyme-like activities, and immunological effect,\nthe Ce SAs@NC platform appears to have tumor specificity, less toxic\nside effects, and a high curative effect both <i>in vitro</i> and <i>in vivo</i>.