Lysosome-Specific Coumarin-Based Fluorescent Bioprobes for in Vivo Polarity Sensing and Cancer Treatment

About 90% of cancer deaths worldwide are caused by the spread of cancer cells from the primary tumor to distant organs (metastasis). Therefore, there is an urgent need for an early diagnosis and treatment before cancer metastasis occurs. Lysosomes have emerged as attractive targets for cancer diagnosis and treatment because polar defects in lysosomes can induce apoptosis and cell death. Coumarin is a known polar-sensitive dye with good biocompatibility; because of this, we constructed two fluorescent probes of coumarin derivatives with the “D−π–A” structure, CouN-1 and CouN-2, through three simple reactions. In molecular design, due to morpholine’s prominent lysosomal targeting characteristics, it was used as both lysosomal targeting motifs and an electron donor (D), while coumarin was used as an electron acceptor (A). The experimental results strongly proved that CouN-1 and CouN-2 have a good linear relationship with the polarity change of Δf = 0.209–0.308. In addition, both in vitro and in vivo imaging results have shown that CouN-1 and CouN-2 can specifically identify and monitor tumor sites. In the cell uptake and apoptosis experiments, the two probes also showed a strong antiproliferation effect on cancer cells. All of these characteristics demonstrated the potential of these two polarity-sensitive biological probes, CouN-1 and CouN-2, in the diagnosis and treatment of cancer.