Microwave-Responsive Edge-Oxidized Graphene for Imaging-Guided Neoadjuvant Thermal Immunotherapy via Promoting Immunogenic Cell Death and Redressing Hypoxia

Immunotherapy has emerged as a promising cancer treatment method. However, it has previously been centered on adjuvant therapy, often falling short as a preoperative treatment of solid cancers, largely attributed to the hypoxic and immunosuppressive microenvironments of untreated tumors. Herein, we develop a multifunctional nanoagent based on edge-oxidized graphene (EOG) for tumor imaging and neoadjuvant thermal immunotherapy. EOG, readily synthesized from selective oxidation and mechanical exfoliation of graphene flakes, exhibits good biocompatibility and remarkable microwave absorption capabilities owing to its large aromatic domains. Consequently, it has demonstrated utility in both microwave-induced thermoacoustic imaging and thermal therapy in a mouse hepatoma model. Furthermore, EOG-based thermal therapy is combined with immunotherapy, which can significantly reduce tumor volume and inhibit tumor growth. A mechanistic study reveals that microwave thermal energy alleviates tumor hypoxia, promotes immunogenic cell death, and ultimately enhances antitumor immune responses. This work pioneers a microwave-based imaging-guided immunotherapy strategy for neoadjuvant treatment of solid tumors and reveals the cell-level pathway of the involved immune suppression.