Image-guided combination chemotherapy and photodynamic therapy using a mitochondria-targeted molecular probe with aggregation-induced emission characteristics

Subcellular targeted cancer therapy and in situ monitoring of therapeutic effect are highly desirable for clinical applications. Herein, we report a series of probes by conjugating zero (TPECM-2Br), one (TPECM-1TPP) and two (TPECM-2TPP) triphenylphosphine (TPP) ligands to a fluorogen with aggregation-induced emission (AIE) characteristics. The probes are almost non-emissive as molecularly dissolved species, but they can light up in cell cytoplasm or mitochondria. TPECM-2TPP is found to be able to target mitochondria, depolarize mitochondria membrane potential and selectively exert potent chemo-cytotoxicity on cancer cells. Furthermore, it can efficiently generate singlet oxygen with strong photo-toxicity upon light illumination, which further enhances its anti-cancer effect. On the other hand, TPECM-1TPP can also target mitochondria and generate singlet oxygen to trigger cancer cell apoptosis, but it shows low cytotoxicity in dark. Meanwhile, TPECM-1TPP can report the cellular oxidative stress by visualizing the morphological changes of mitochondria. However, TPECM-2Br does not target mitochondria and shows no obvious anticancer effect either in dark or under light illumination. This study thus highlights the importance of molecular probe design, which yields a new generation of subcellular targeted molecular theranostic agents with multi-function, such as cancer cell imaging, chemotherapy, photodynamic therapy, and in situ monitoring of the therapeutic effect in one go.