MXene-based mild potothermal therapy synergizes STING activation to enhance the efficacy of cancer vaccines post-cryoablation

Cryoablation (CRA) is a clinical treatment modality for minimally invasive local tumor ablation. Rare clinical reports have shown that CRA can induce a cryoimmune effect and enhance systemic anti-tumor immunity against potential metastases, a phenomenon known as the “abscopal effect”. Here, we innovatively propose a sequential treatment strategy to improve the tumor immune microenvironment by activating the cGAS-STING signaling pathway of immune cells and mild photothermal therapy (mPTT) before CRA, making this rare but exciting phenomenon more reproducible. Specifically, we designed functional nanosheets (Ti 3 C 2 @Au-PEG-DMXAA) based on Ti 3 C 2 MXene, with gold nanoparticles attached to the surface, PEGylated, and loaded with the STING agonist (DMXAA). Due to the attachment of gold nanoparticles, CT-guided visual injection of the functional nanosheets was achieved. The synergistic effect of mPTT and STING pathway activation promoted the immunogenic death of tumor cells, activation of dendritic cells, repolarization of tumor-associated macrophages, and enrichment of cytotoxic T cells in the tumor microenvironment. Subsequently, sequential CRA eradicated local “hot” tumors, initiating a “cancer vaccines” effect through the in-situ gradual release of tumor-associated antigens, boosting systemic anti-tumor immunity, and effectively generating long-term immune memory, thereby inhibiting tumor recurrence and distant metastases.