Mitochondrial targeting ratiometric theranostic probe activated by hydrogen peroxide toward tracking pH variations in therapeutic processes.

BACKGROUND: At present, cancer remains one of the most devastating health challenges worldwide. Its high mortality rate, metastatic potential, and resistance to conventional treatments make it particularly lethal. Under these circumstances, developing comprehensive theranostic probe that can combine precise tumor detection with efficient treatment has become an urgent priority. Particularly, activatable theranostic probe that can dynamically monitor the changes of cells during the treatment intervention process has become a new research hotspot, bringing hope for more accurate diagnosis and effective treatment.

RESULTS: In this work, we constructed an activatable theranostic probe RF-HPQ-HP using delocalized lipophilic cations as mitochondrial targeting groups, boric ester (H2O2 recognition group) as a "switch" for diagnosis and treatment of tumor cells, and insoluble group HPQ which can cause cellular oxidative stress as a toxic motif. The probe RF-HPQ-HP can enter tumor cells by targeting mitochondria through mitochondrial membrane potential, and then high H2O2 content will change the fluorescence and simultaneously release insoluble dye RF-HPQ in the cells, thereby triggering subsequent reactions. Cell experiments have shown that the insoluble dye RF-HPQ can not only exploit the selective high toxicity to tumor cells through oxidative stress, but also track pH fluctuations of mitochondrial, meaning that it has the potential to track changes in cell state.

SIGNIFICANCE: This study not only provides a new strategy for the design of activatable theranostic probe with organelle-targeting capabilities, but also establishes a novel method for monitoring dynamic cellular state changes during tumor treatment. The proposed approach shows potential to cancer diagnosis and treatment by enabling simultaneous imaging and therapeutic monitoring.