Mechanistic study of tumor fluorescence response signals based on a near-infrared viscosity-sensitive probe

Viscosity is an important physiological parameter closely associated with various cellular processes and diseases. Several fluorescence probes responsive to viscosity have been developed, demonstrating high sensitivity specifically towards tumor tissues. However, the underlying core mechanism of this highly potential responsive signal has been a subject of debate, as highly sensitive probes encounter excessive environmental interferences in complex tumor tissues. Therefore, we have developed a viscosity-responsive fluorescence probe based on the classical TICT mechanism (twisted intramolecular charge transfer) as a research tool. This probe features an ultra-wide emission range of 700-1200 nm in the near-infrared spectrum, strong photostability, and simultaneous targeting of mitochondria and lysosomes. Through in-depth analysis, we have revealed the intrinsic mechanisms underlying its functionality, demonstrating that the major contributor to the fluorescence change of responsive probes during imaging is the inherent state of cells rather than the tumor microenvironment or the cell type. Our findings provide a theoretical foundation for the continued exploration and application of viscosity-responsive probes.