Apoptotic Induction of Mitochondria-Anchored Aggregation-Induced Emission Luminogens through the Intrinsic Mitochondrial Pathway

[Image: see text] Gastric cancer has the third highest mortality rate globally. Chemotherapy is the primary treatment used in advanced gastric cancer. Aggregation-induced emission luminogens (AIEgens) have been exploited as non-toxic and efficient chemotherapy agents for the treatment of cancer. Our previous research demonstrated that tetraphenylethene-substituted pyridinium salt (TPE-Py) is a kind of AIEgen that had the ability to lead to apoptosis in gastric cancer cells. However, it is currently unknown whether TPE-Py induced apoptosis in gastric cancer cells by the mitochondria-mediated pathway. This research confirmed that TPE-Py could target mitochondria and induce apoptotic cell death. In addition, several well-recognized indicators were detected to investigate the functional and morphological changes of mitochondria. We found that TPE-Py could diminish the mitochondrial membrane potential and increase the accumulation of reactive oxygen species and the discharge of cytochrome c, which was related to the mitochondrial apoptotic pathway. Meanwhile, morphological changes in mitochondria were also observed by transmission electron microscopy in gastric cancer cells after incubation with TPE-Py. In conclusion, we provided insights into the mechanism regulating apoptosis in gastric cancer cells and elucidated the mechanism of apoptosis induced by TPE-Py via the intrinsic mitochondrial pathway.