用于与格列本脲协同肿瘤消融的内质网靶向聚集诱导发光发光体

Endoplasmic Reticulum-Targeted Aggregation-Induced Emission Luminogen for Synergetic Tumor Ablation with Glibenclamide.

作者信息

Wu Yifan, Chen Xiaohui, Zhu Liwei, Wang Deliang, Li Xue, Song Jiayi, Wang Dong, Yu Xiyong, Li Ying, Tang Ben Zhong

机构信息

Center for AIE Research, Shenzhen Key Laboratory of Polymer Science and Technology, Guangdong Research Center for Interfacial Engineering of Functional Materials, College of Materials Science and Engineering, Shenzhen University, Shenzhen, Guangdong 518060, China.

Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Physics and Optoelectronic Engineering, Shenzhen University, Shenzhen, Guangdong 518060, China.

出版信息

ACS Appl Mater Interfaces. 2023 Oct 30. doi: 10.1021/acsami.3c10940.

DOI:10.1021/acsami.3c10940

PMID:37903083

Abstract

Photodynamic therapy based on fluorescence illumination of subcellular organelles and bursts of reactive oxygen species (ROS) has been recognized as a promising strategy for cancer theranostics. However, the short life of ROS and unclarified anticancer mechanism seriously restrict the application. Herein, we rationally designed and facilely synthesized a 2,6-dimethylpyridine-based triphenylamine (TPA) derivative TPA-DMPy with aggregation-induced emission (AIE) features and production of type-I ROS. Except for its selective binding to the endoplasmic reticulum (ER), TPA-DMPy, in synergy with glibenclamide, a medicinal agent used against diabetes, induced significant apoptosis of cancer cells and . Additionally, TPA-DMPy greatly incited the release of calcium from ER upon light irradiation to further aggravate the depolarization of ER membrane potential caused by glibenclamide, thus inducing fatal ER stress and crosstalk between ER and mitochondria. Our study extends the biological design and application of AIE luminogens and provides new insights into discovering novel anticancer targets and agents.

摘要

基于亚细胞器荧光照明和活性氧（ROS）爆发的光动力疗法已被认为是一种有前途的癌症诊疗策略。然而，ROS的短寿命和不明的抗癌机制严重限制了其应用。在此，我们合理设计并简便合成了一种具有聚集诱导发光（AIE）特性和I型ROS产生能力的基于2,6-二甲基吡啶的三苯胺（TPA）衍生物TPA-DMPy。除了其与内质网（ER）的选择性结合外，TPA-DMPy与一种用于治疗糖尿病的药物格列本脲协同作用，诱导癌细胞发生显著凋亡。此外，TPA-DMPy在光照下极大地促使内质网释放钙，进一步加剧格列本脲引起的内质网膜电位去极化，从而诱导致命的内质网应激以及内质网与线粒体之间的相互作用。我们的研究扩展了AIE发光体的生物学设计和应用，并为发现新的抗癌靶点和药物提供了新的见解。