Ratiometric NIR Cell Membrane-targeted Probe for Monitoring Cell Membrane Polarity and Tumor Application

The investigation of cell membrane polarity is critical to determining cell physiological states and related disease for diagnosis and treatment. Herein, a ratiometric NIR cell membrane-targeted fluorescent probe, Cy-C12-MpN, was designed and synthesized to assess cell membrane polarity, which has an amphiphilic structure consisting of a dodecyl unit and a quaternary ammonium unit. It exhibited changes in emission wavelength and fluorescence intensity with the changes in polarity of the solution. It can use the ratio signal of the two peaks to report the polarity difference in its environment. The self-tuning of the probe internal system ensures the reliability of the test results and can be a semi-quantitative detection method. Indeed, in vitro polarity test, the ratio signal reported by Cy-C12-MpN had an optimal linear range with respect to polarity. Cell imaging illustrated the excellent cell membrane-targeted ability of Cy-C12-MpN, as it can rapidly target the cell membrane within 30 s and still anchor at it well after 1 hr. Moreover, Cy-C12-MpN showed that cell membrane polarity decreases after cells become cancerous, and observed the changes in cell membrane polarity caused by homeostatic membrane response stimulated by polyunsaturated fatty acids firstly. Imaging in vivo demonstrated the ability of Cy-C12-MpN to distinguish between tumor cells and normal cells, and further demonstrated that tumor cells have lower cell membrane polarity. In summary, the accuracy of the ratio detection of the probe Cy-C12-MpN and its excellent cell membrane targeting ability reveal reliable results that can provide very useful insights for cancer research.