Zhang Liang, Guo Fuding, Xu Saiting, Deng Qiang, Xie Mengjie, Sun Jianwei, Kwok Ryan T K, Lam Jacky W Y, Deng Hexiang, Jiang Hong, Yu Lilei, Tang Ben Zhong
Department of Chemistry and The Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, 999077, China.
Department of Cardiology, Renmin Hospital of Wuhan University, Institute of Molecular Medicine, Renmin Hospital of Wuhan University, Hubei Key Laboratory of Autonomic Nervous System Modulation, Hubei Key Laboratory of Cardiology, Cardiovascular Research Institute, Wuhan University, Cardiac Autonomic Nervous System Research Center of Wuhan University, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan University, Jiefang Road, Wuhan, 430060, China.
Adv Mater. 2023 Aug 2:e2304620. doi: 10.1002/adma.202304620.
The engineering of aggregation-induced emission luminogens (AIEgen) based covalent organic frameworks (COFs), TDTA-COF, BTDTA-COF, and BTDBETA-COF are reported, 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 neuroinflammation 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 neuroinflammation peri-SG microenvironment and offering myocardial and arrhythmia protection. The work on AIE COF-based hyperthermia agent for VAs inhibition provides a new avenue for mitigating cardiac sympathetic nerve hyperactivity.
报道了基于聚集诱导发光发光体（AIEgen）的共价有机框架（COF），即TDTA-COF、BTDTA-COF和BTDBETA-COF的工程设计，作为抑制恶性室性心律失常（VA）发生的热疗剂。这些AIE COF具有双重功能，它们不仅通过局部热疗（LHT）直接调节星状神经节（SG）的功能和神经活动，还能诱导白色脂肪褐变并改善SG周围微环境中的神经炎症，这有利于抑制缺血诱导的VA。体内研究证实，BTDBETA-COF介导的LHT增强了产热和褐变相关基因的表达，从而在对抗VA中发挥协同作用。对SG周围脂肪组织的转录组分析显示炎症细胞因子大幅下调，突出了BTDBETA-COF介导的LHT在改善SG周围微环境中的神经炎症以及提供心肌和心律失常保护方面的效力。基于AIE COF的VA抑制热疗剂的研究为减轻心脏交感神经亢进提供了一条新途径。
