The single-atom iron nanozyme mimicking peroxidase remodels energy metabolism and tumor immune landscape for synergistic chemodynamic therapy and photothermal therapy of triple-negative breast cancer

Chemotherapy, as one main strategy to relieve tumor progression, has a weak effect on triple-negative breast cancer (TNBC) chest wall metastasis. The development of near-infrared (NIR) light-responsive nanomaterials for chemodynamic therapy (CDT) and photothermal therapy (PTT) is a promising platform but still challenging in biomedicine. This study reports a peroxidase mimicking nanozyme (Fe-N-C SAzyme) against TNBC by CDT and PTT. Fe-N-C SAzyme generated reactive oxygen species (ROS) by decomposing H2O2 into hydroxyl radicals (•OH) and also induced light-to-heat conversion under the exposure of 808 nm laser irradiation. With these biological characteristics, the obtained Fe-N-C SAzymes displayed enhanced cell cytotoxicity and inhibition of cancer cell proliferation both in vitro and in vivo at a low dose of nanoagent and a moderate NIR laser power density. Besides, Fe-N-C nanoagent with its excellent ROS generation brought metabolic reprogramming of elevated glycolysis in tumor cells. In vivo experiments, when combined with PTT, the enhanced antitumor effect was found by the elimination of M-MDSC in tumor microenvironment. Fe-N-C SAzymes can serve as a new synergistic CDT and PTT nanoagent to simultaneously reprogram tumor metabolism and tumor microenvironment. It will provide prospects for chemodynamic/photothermal combined cancer therapy for TNBC chest wall metastasis based on the use of a single nanosystem.