Nanoscale covalent organic framework-mediated pyroelectrocatalytic activation of immunogenic cell death for potent immunotherapy

The conventional molecular immunogenic cell death (ICD) inducers suffer from poor biocompatibility and unsatisfactory efficacy. Here, a biocompatible nanosized covalent organic framework (nCOF)-based pyroelectric catalyst (denoted as TPAD-COF NPs) is designed for pyroelectric catalysis-activated in situ immunotherapy. TPAD-COF NPs confine organic pyroelectric molecules to rigid TPAD-COF NPs to substantially reduce aggregation and enhance biocompatibility, thus improving pyroelectrocatalytic efficiency. After tumor internalization, TPAD-COF NPs facilitate photothermal tumor ablation under near-infrared (NIR) laser exposure, resulting in effective ICD induction. In addition, TPAD-COF NPs effectively catalyze the conversion of temperature changes to pyroelectric changes, which subsequently react with adjacent O₂ to generate reactive oxygen species, thus triggering robust ICD activation. In vivo evaluation using mouse models confirmed that TPAD-COF NPs evidently inhibited the proliferation of primary and distant tumors and prevented lung metastasis under NIR laser illumination. Therefore, this study opens an avenue for designing nCOF-based catalysts for pyroelectric catalysis-activated in situ immunotherapy.