Design and application of prodrug fluorescent probes for the detection of ovarian cancer cells and release of anticancer drug.

Ovarian cancer is a gynecologic malignancy with high mortality. The main reason is that it is detected at an advanced stage due to a lack of early diagnosis and treatment. Therefore, it is of great interest to develop a chemical tool that can visualize ovarian cancer cells in real-time and eliminate them. Unfortunately, probes that can simultaneously monitor both modes of action for the diagnosis and treatment of ovarian cancer have not been developed. Here, we designed a novel prodrug fluorescent probe (YW-OAc) that not only visually tracks cancer cells but also enables the on-demand delivery of chemotherapeutic agents. By ß-Gal-mediated glycosidic bond hydrolysis, the fluorescent signal changed from blue to green (signal 1), enabling visual tracking of ovarian cancer cells. Subsequently, the identified cancer cells were subjected to precise light irradiation to induce anticancer drug release accompanied by a fluorescence transition from green to blue (signal 2), enabling real-time information on drug release. Thus, the prodrug fluorescent probe YW-OAc provides comprehensive two-step monitoring during cancer cell recognition and clearance. Notably, YW-OAc exhibited high affinity (Km = 3.74 µM), high selectivity, and low detection limit for ß-Gal (0.0035 U/mL). We also demonstrated that YW-OAc can visually trace endogenous ß-Gal in different cells and exhibit high phototoxicity in ovarian cancer cells. We hope that the prodrug fluorescent probe YW-OAc, can be used as an effective tool for biomedical diagnosis and treatment.

Fast and sensitive near-infrared ratiometric fluorescent probe with a self-immolative spacer for imaging of endogenous alkaline phosphatase activity in cells and in vivo.

Alkaline phosphatase (ALP), a vital hydrolase widely distributed in organisms, is regarded as a critical biomarker strongly associated with many physiological and pathological processes. Therefore, fast and efficient detection of ALP activity in vivo is of great value for clinical diagnosis. Herein, a novel near-infrared (NIR) ratiometric fluorescent probe (HP) was designed based on ESIPT for trapping ALP activity in cells and in vivo. Notably, incorporating a self-immolative spacer dramatically reduces the response time (8.5 min) of HP. Moreover, the probe exhibits excellent water solubility, large Stokes shift (147 nm), the ratiometric determination of ALP at 570 nm and 689 nm, low detection limit (3.98 U L-1). More importantly, the probe was also successfully applied to detect and monitor variations in endogenous ALP activity in zebrafish due to the drug (APAP) induced organ damages.