Two Water-Soluble and Wash-Free Fluorogenic Probes for Specific Lighting Up Cancer Cell Membranes and Tumors

The construction of microenvironment-sensitive probes with good cell membrane-targetability can reveal the fundamental properties of cell membranes. Herein, two polarity-sensitive probes, termed MEMs were reported for the first time to specifically light up cancer cell membranes. Both probes were designed with tetrahydroquinoxaline coumarin amide as the fluorophore, and quaternary ammonium groups were appended to increase water solubility and target cell membranes. In vitro studies showed that the fluorescence of both probes displayed strong polarity dependence and had a wide linear range to polarity (Δf). MEMs also displayed excellent cell membrane targeting ability and could long-term light up cell membranes with red fluorescence and a wash-free process. More excitingly, MEMs could specifically light up cancer cell membranes, revealing that cancer cells might have lower cell membrane polarity than normal cells. In vivo studies showed that MEMs could also effectively distinguish tumors from normal tissues. Overall, this work has not only developed two polarity-sensitive probes with good cell membrane targetability, but also provided new insights and methods for an in-depth understanding of cancer cells and cancer diagnosis.