Endoplasmic reticulum targeted photosensitizer with high photostability and dual ROS generation for breast cancer PDT via apoptosis and pyroptosis.

In tumor photodynamic therapy, the development of theranostic probes with favorable targeting capability, biocompatibility, and high photosensitizing activity is essential for enhancing therapeutic precision and efficacy. However, most existing probes are limited by insufficient targeting and an imbalance between phototoxicity and biosafety. In this study, we synthesized a biocompatible luminogen (compound 3), which can be applied to pH sensing, non-invasive imaging, and tumor photodynamic therapy. It exhibited excellent biocompatibility, specificity to the endoplasmic reticulum, photostability, and long-term imaging ability owing to high photostability and high tissue penetration . Furthermore, compound 3 could rapidly infiltrate living zebrafish embryos through the eggshell and penetrate the deeper layers. Moreover, compound 3 exhibits excellent imaging performance under two-photon excitation. Finally, compound 3 kills cancer cells by inducing apoptosis, pyroptosis, and immunogenic cell death under low-power white light irradiation. In the experiments, tumor tissues were eliminated with only one dose of photodynamic therapy treatment, positioning it an ideal photosensitizer candidate for photodynamic therapy.