A near-IR ratiometric fluorescent probe for the precise tracking of senescence: a multidimensional sensing assay of biomarkers in cell senescence pathways

Senescence is a complex physiological process that can be induced by a range of factors, and cellular damage caused by reactive oxygen species (ROS) is one of the major triggers. In order to learn and solve age-related diseases, tracking strategies through biomarkers, including senescence-associated β-galactosidase (SA-β-gal), with high sensitivity and accuracy, have been considered as a promising solution. However, endogenous β-gal accumulation is not only associated with senescence but also with other physiological processes. Therefore, additional assays are needed to define cellular senescence further. In this work, a fancy fluorescent probe SA-HCy-1 for accurately monitoring senescence is developed, with SA-β-gal and HClO as targets under high lysosomal pH conditions (pH > 6.0) specifically, on account of the role β-gal commonly played as an ovarian cancer biomarker. Therefore, precise tracking of cellular senescence could be achieved in view of these three dimensions, with response in dual fluorescence channels providing a ratiometric sensing pattern. This elaborate strategy has been verified to be suitable for biological applications by skin photo-aging evaluation and cellular passage tracing, displaying a significantly improved sensitivity compared with the commercial X-gal kit measurement.