Rational design of hypochlorous acid-activatable fluorescent probe for diagnostic imaging and therapeutic evaluation...

The recurrent breast cancer (BC) has elicited significant concern due to its rising recurrence rates and associated mortality. However, there is currently no effective detection method to mitigate the deterioration of BC recurrence. The imbalance of HClO content could lead to oxidative stress in the body, which damaging host tissues. Additional, improper regulation of HClO may exacerbate the progression of BC and promote the metastasis of BC cells. Accurately diagnosing and monitoring the HClO levels is crucial for treating BC recurrence. Traditional fluorescent probes for HClO exhibit several limitations, including poor selectivity, susceptibility to photobleaching, a small Stokes shift, and vulnerability to disturbances from excitation and fluorescence self-absorption, which undermine the precise detection of target analytes and restrict their biological applications. Herein, rational designed hypochlorous acid-activatable fluorescent probe (QPIO) was synthesized based on phenothiazine (PZ), quinoline malononitrile (QM), and hemicyanine, which demonstrated high anti-interference capability and a significant Stokes shift for HClO detection. Under various stimuli, QPIO was able to monitor HClO levels in RAW 264.7 and 4T1 cells in the red channel. Furthermore, it elucidated the correlation between HClO concentration and the progression of BC recurrence. Consequently, QPIO was utilized to diagnose recurrent BC, track therapeutic progress, and monitor the recurrence status of breast tumors in mouse models through in vivo HClO fluorescence imaging. It was demonstrated that a close relationship exists between the dynamic changes in HClO levels and BC recurrence, potentially advancing the understanding of the early diagnosis and development of therapeutic agents for recurrent BC.