AIEgen-based Covalent Organic Frameworks for Preventing Malignant Ventricular Arrhythmias Via Local Hyperthermia Therapy.

We report the engineering of aggregation-induced emission luminogens (AIEgen) based covalent organic frameworks (COFs), TDTA-COF, BTDTA-COF, and BTDBETA-COF, as hyperthermia agents for inhibiting the occurrence of malignant ventricular arrhythmias (VAs). These AIE COFs exhibit dual functionality, as they not only directly modulate the function and neural activity of stellate ganglion (SG) through local hyperthermia therapy (LHT) but also induce the browning of white fat and improve the neuro-inflammation peri-SG microenvironment, which is favorable for inhibiting ischemia-induced VAs. In vivo studies have confirmed that BTDBETA-COF-mediated LHT enhances thermogenesis and browning-related gene expression, thereby serving a synergistic role in combating VAs. Transcriptome analysis of peri-SG adipose tissue reveals a substantial downregulation of inflammatory cytokines, highlighting the potency of BTDBETA-COF-mediated LHT in ameliorating the neuro-inflammation peri-SG microenvironment and offering myocardial and arrhythmia protection. Our work on AIE COF-based hyperthermia agent for VAs inhibition providing a new avenue for mitigating cardiac sympathetic nerve hyperactivity. AIEgen; covalent organic frameworks; hyperthermia agent; malignant ventricular arrhythmias; neuromodulation This article is protected by copyright. All rights reserved.