In Situ Redox of TiSe2 Nanoplates to Excite Chemodynamic‐Enhanced Cancer Sono‐Immunotherapy

Abstract

Different from the direct delivery of chemodynamic agents into tumor tissue for chemodynamic therapy (CDT), this work reports the fabrication of heterojunction sonosensitizers (CD/TiSe2) for the in situ generation of chemodynamic agents by responding to tumor microenvironment (TME), realizing the in situ CDT‐enhanced sono‐immunotherapy. The in situ redox of TiSe2 in acidic TME leads to the formation of TiOxSe2−x containing Se (0), selenate, and Ti3+/Ti4+ redox couple, which can facilitate in situ CDT through a Ti3+‐mediated Fenton‐like reaction and consume overexpressed glutathione (GSH) via a Ti4+‐mediated GSH depletion. Moreover, Se ions generated through the in situ redox process promote the maturation of dendritic cells, consequently activating the adaptive immune responses. In another aspect, the construction of heterojunctions within carbon dots and TiSe2 improves the reactive oxygen species (ROS) generation efficiency of TiSe2 in a cascaded manner, which enhances the sonodynamic activity and amplifies the chemodynamic performance. More importantly, the ROS produced by in situ CDT and sonodynamic therapy efficiently triggers immunogenic cell death through a synergistic therapy based on the elicitation of antitumor immunity with the aid of an immune checkpoint blockade. This work thus provides a distinct paradigm of transition metal selenide‐originated in situ Fenton‐like agent generation for in situ CDT‐enhanced sono‐immunotherapy.