A Two-Photon Probe Based on Naphthalimide-Styrene Fluorophore for the Tracking of Cellular Senescence.

Cellular senescence is a state of stable cell cycle arrest that can negatively affect the regenerative capacities of tissues and can contribute to inflammation and the progression of various aging-related diseases. Advances in the detection of cellular senescence are still crucial to monitor the action of senolytic drugs and to assess the early onset or accumulation of senescent cells. Here, we describe a naphthalimide-styrene-based probe () for the detection of cellular senescence both and . is hydrolyzed by the increased lysosomal β-galactosidase activity of senescent cells, resulting in fluorescence emission. The probe was validated using normal human fibroblasts and various cancer cell lines undergoing senescence induced by different stress stimuli. Remarkably, was also validated in an orthotopic breast cancer mouse model treated with senescence-inducing chemotherapy and in a renal fibrosis mouse model. In all cases, allowed the unambiguous detection of senescence as well as in tissues and tumors . This work is expected to provide a potential technology for senescence detection in aged or damaged tissues.