Cellular senescence is a mechanism by which a cell enters stable cell cycle arrest triggered by various types of stress such as telomere shortening, oxidative stress and DNA damage. It is implicated in a number of pathophysiological conditions including age-related diseases, degenerative disorders and cancer. Despite its importance, the current toolbox for studying or monitoring senescence in vivo is limited. We have developed a series of novel near-infrared (NIR) fluorescent probes that can be activated by senescence-associated β-galactosidase (SA-β-Gal) and self-immobilize onto intracellular proteins via in situ labeling. We compared the labeling efficiency of these probes in various senescence models including chemotherapy and radiation-induced senescence in cells and in live animals. The results show that by modulating the leaving group, we can tune the non-specific uptake, labeling efficiency, and their prolonged retention at the site of activation. These probes can be used for imaging of senescence developed in live cells, as well as long-term tracking of senescent cells in various animal models.

NIR fluorescent probes for in vivo senescence imaging via tunable in situ labeling

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