Monitoring Cell Plasma Membrane Polarity by a NIR Fluorescence Probe with Unexpected Cell Plasma Membrane-Targeting Ability

[Image: see text] The cell plasma membrane, the natural barrier of a cell, plays critical roles in a mass of cell physiological and pathological processes. Therefore, revealing and monitoring the local status of the cell plasma membrane are of great significance. Herein, using a near-infrared (NIR) fluorescence probe BTCy, microenvironmental polarity in the cell plasma membrane was in situ monitored. BTCy showed sensitive and selective fluorescence decrease response at 706 nm with the increase of polarity as its polarity-responsive D−π–A structure. Most importantly, BTCy showed unexpected cell plasma membrane-targeting ability, probably due to its amphiphilic structure. With BTCy, the distinguishing imaging of cancer and normal cells was done, in which cancer cells exhibited significantly stronger signals due to their lower cell plasma membrane polarity. In addition, with the imaging of BTCy, the ferroptosis process was revealed with no significant cell plasma membrane polarity variation for the first time. Furthermore, BTCy was employed for in vivo imaging of tumor tissue in the 4T1-tumor-bearing mice. The polarity-responsive and cell plasma membrane-targeting properties of BTCy make it a useful tool for monitoring cell plasma membrane polarity variation, providing an efficient and simple method for tumor diagnosis.