Abstract
Nitroreductase (NTR) is a frequently used biomarker for the assessment of hypoxia level in tumors. As one of the main sources of enzymes, the dysfunction of lysosomes typically leads to various diseases. In this study, an NTR-triggered lysosome-targeting probe, M-TPE-P, was designed based on a tetraphenylethylene core. DFT calculation indicated that the probe possessed a narrow singlet–triplet energy gap (ΔEST), rendering it an efficient photosensitizer. The docking affinity of M-TPE-P to NTR revealed a strong structural match between them. Photophysical properties demonstrated that the probe exhibited high selectivity and sensitivity in a broad pH rang for detecting NTR. The detection limit was determined to be 53.6 ng/mL in 80% PBS/DMSO solution. Cell imaging studies showed the probe could trace intracellular NTR behavior with green fluorescence. The colocalization analysis indicated its excellent lysosome-targeting specificity, with a Pearson correlation coefficient of 0.97. In addition, the probe exhibited effective ROS generation ability and a significant PDT effect after NIR irradiation, positioning it as a promising photosensitizer for cancer treatment.
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