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

Abstract

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.