Long-Term Imaging Probe for Monitoring the Changes of Cell Membrane Viscosity and Its Application in Diabetes Nephropathy.

Cell membrane (CM) viscosity is an important parameter indicating the state of cells, and the development of fluorescent probes capable of detecting CM viscosity is of great significance for cell research and disease diagnosis. However, most developed CM probes cannot achieve long-term imaging because they are easily internalized into cells, resulting in short imaging durations and gradual signal loss. In addition, CM probes for disease diagnosis are largely unexplored. Herein, we report three novel viscosity-sensitive CM probes (LT-M, LT-S, and LT-N). Among them, LT-M contains a rigid and steric quaternary ammonium salt, enabling it to achieve long-term (>12 h) imaging of CMs and sensitive detection of CM viscosity. LT-M shows a long emission wavelength (641 nm), large Stokes shift (121 nm), rapid and wash-free imaging performance, and good photostability. With these characteristics, LT-M successfully achieved effective differentiation between cancer cells and normal cells, and sensitively detected the increase of CM viscosity under conditions such as ferroptosis and hyperglycemia stimulation. More importantly, in vivo mouse imaging showed that LT-M could target the kidney and revealed an increased renal viscosity in diabetes, which provided a valuable new detection method for the diagnosis and evaluation of diabetes nephropathy.