An endoplasmic reticulum targeted NIR-AIE fluorescent probe with superior photostability for accelerating oxidative stress to trigger cancer cells apoptosis

Targeting the organelles that generate oxidative stress and implementing oxidative stress therapy is an essential and ambitious task. As an important subcellular organelle in eukaryotic cells, the endoplasmic reticulum (ER) is significant in mediating the direction of cell metabolism and apoptosis. To achieve the goal, we rationally designed and synthesized a photosensitizer named TTQ-ER with aggregation-induced emission (AIE) characteristics. Such a probe connects the AIE-fluorophore to the glibenclamide backbone, which enables TTQ-ER to specifically target the ER and promote emission in the near-infrared region, avoiding the negative impact of autofluorescence in organisms. Meanwhile, TTQ-ER has a large stokes shift, excellent anti-photobleaching properties, and sufficient 1O2 production (8.85-fold of Ce6). Apoptosis assay and cell migration assay further verified that excessive reactive oxygen species production by TTQ-ER in cancer cells could promote oxidative stress in the ER microenvironment and disrupt the normal biological function of ER, thus causing elevated local lipid peroxidation and inducing apoptosis in cancer cells. Consequently, this work offers informative ideas for designing a newly generation of photosensitizers to achieve accurate photodynamic therapy.