Enhanced Tumor Ablation and Immune Activation Via Irreversible Electroporation and Functionalized Vermiculite Nanosheets

Abstract Irreversible electroporation (IRE) is a minimally invasive, non‐thermal tumor ablation technique that induces nanoscale membrane perforation, leading to immunogenic cell death (ICD). However, IRE alone is limited by uneven electric field attenuation, incomplete tumor ablation, and the immunosuppressive nature of the tumor microenvironment. To address these challenges, a multifunctional nanomaterial, vermiculite nanosheets/calcium peroxide nanosheets (VMT/CaO₂ NSs), is developed to enhance the efficacy of IRE. VMT/CaO₂ NSs exhibit a high specific surface area, intrinsic catalytic properties, and strong adsorption capacity, enabling them to adsorb antigens and damage‐associated molecular patterns released during IRE. This transforms the tumor site into an in situ tumor vaccine, promoting dendritic cell (DC) activation and enhancing antigen presentation. The catalytic activity of VMT/CaO₂ NSs generates reactive oxygen species through Fenton‐like reactions, amplifying oxidative stress to eliminate residual tumor cells and modulate the dense extracellular matrix of the TME, improving immune cell infiltration. In vitro and in vivo studies demonstrate that the combination of VMT/CaO₂ NSs with IRE significantly enhances tumor ablation, immune activation, and systemic antitumor immunity. The treatment effectively induces ICD, activates cytotoxic T lymphocytes (CD8⁺ T cells), and generates memory T cells, ensuring durable immune surveillance and reducing the likelihood of recurrence.