Abstract

Purpose Reactive oxygen species (ROS) are a group of signaling biomolecules that play important roles in the cell cycle. When intracellular ROS homeostasis is disrupted, it can induce cellular necrosis and apoptosis. It is desirable to effectively cascade-amplifying ROS generation and weaken antioxidant defense for disrupting ROS homeostasis in tumor microenvironment (TME), which has been recognized as a novel and ideal antitumor strategy. Multifunctional nanozymes are highly promising agents for ROS-mediated therapy.Methods This study constructed a novel theranostic nanoagent based on PEG@Cu2-xS@Ce6 nanozymes (PCCNs) through a facile one-step hydrothermal method. We systematically investigated the photodynamic therapy (PDT)/photothermal therapy (PTT) properties, catalytic therapy (CTT) and glutathione (GSH) depletion activities of PCCNs, antitumor efficacy induced by PCCNs in vitro and in vivo.Results PCCNs generate singlet oxygen (1O2) with laser (660 nm) irradiation and use catalytic reactions to produce hydroxyl radical (•OH). Moreover, PCCNs show the high photothermal performance under NIR II 1064-nm laser irradiation, which can enhance CTT/PDT efficiencies to increase ROS generation. The properties of O2 evolution and GSH consumption of PCCNs achieve hypoxia-relieved PDT and destroy cellular antioxidant defense system respectively. The excellent antitumor efficacy in 4T1 tumor-bearing mice of PCCNs is achieved through disrupting ROS homeostasis-involved therapy under the guidance of photothermal/photoacoustic imaging.Conclusion Our study provides a proof of concept of “all-in-one” nanozymes to eliminate tumors via disrupting ROS homeostasis.