Abstract

Fluorescence-guided photodynamic therapy (PDT) is regarded as a promising strategy for precise cancer treatment by making use of photosensitizers (PSs) with reactive oxygen species (ROS) generation.1 Some efficient PSs have been reported in recent years2,3 but multifunctional PSs that are responsive to cancer-specific biomarkers are rarely reported. In this study, we introduced a phosphate group as a cancer-specific biomarker of alkaline phosphatase (ALP)4 on a PS with the features of aggregation-induced emission (AIE)5 for cancer cell imaging and therapy. In the cancer cells with high ALP expression, the phosphate group on the AIE probe is selectively hydrolyzed by ALP. Consequently, the probe residue is aggregated and gives a “turn on” fluorescent response. Moreover, fluorescence-guided PDT was realized by the aggregates of probe residue with strong ROS generation efficiency under white light irradiation. Overall, this work presents a novel strategy of applying ALP-responsive AIE PS for specific imaging cancer cells. 

Scheme 1.  Schematic illustration of the hydrolysis of TPAPyP by intracellular ALP in cancer cells and the subsequent photodynamic reaction of TPAPy under white light irradiation.

Reference:

1. Zhou, Z.; Song, J.; Nie, L.; Chen, X., Reactive oxygen species generating systems meeting challenges of photodynamic cancer therapy. Chem. Soc. Rev. 2016, 45 (23), 6597-6626.
2. Liu, S.; Feng, G.; Tang, B. Z.; Liu, B., Recent advances of AIE light-up probes for photodynamic therapy. Chemical science 2021, 12 (19), 6488-6506.
3. Hu, F.; Xu, S.; Liu, B., Photosensitizers with aggregation‐induced emission: materials and biomedical applications. Adv. Mater. 2018, 30 (45), 1801350.
4. Rao, S.; Snaith, A.; Marino, D.; Cheng, X.; Lwin, S.; Orriss, I.; Hamdy, F.; Edwards, C., Tumour-derived alkaline phosphatase regulates tumour growth, epithelial plasticity and disease-free survival in metastatic prostate cancer. Br. J. Cancer 2017, 116 (2), 227-236.
5. Mei, J.; Leung, N. L.; Kwok, R. T.; Lam, J. W.; Tang, B. Z., Aggregation-induced emission: together we shine, united we soar! Chem. Rev. 2015, 115 (21), 11718-11940.