基于亚细胞器荧光照明和活性氧（ROS）原位爆发的光动力疗法已被认为是癌症治疗诊断学的一种有前途的策略。然而，ROS的寿命短和抗癌机制尚不明确，严重限制了其应用。在此，我们合理设计并轻松合成了一种基于2,6-二甲基吡啶的三苯胺（TPA）衍生物TPA-DMPy，具有聚集诱导发射（AIE）特征并产生I型ROS。除了与内质网（ER）选择性结合外，TPA-DMPy 与抗糖尿病药物格列本脲协同作用，可在体外和体内诱导癌细胞显着凋亡。此外，TPA-DMPy在光照射下会极大地刺激内质网钙的释放，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串扰。我们的研究扩展了 AIE 发光剂的生物设计和应用，并为发现新型抗癌靶点和药物提供了新的见解。

Photodynamic therapy based on fluorescence illumination of subcellular organelles and in situ 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 in vitro and in vivo. 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.