Dipeptidylpeptidase‐4‐targeted activatable fluorescent probes visualize senescent cells

Abstract Senescent cells promote cancer development and progression through chronic inflammation caused by a senescence‐associated secretory phenotype (SASP). Although various senotherapeutic strategies targeting senescent cells have been developed for the prevention and treatment of cancers, technology for the in vivo detection and evaluation of senescent cell accumulation has not yet been established. Here, we identified activatable fluorescent probes targeting dipeptidylpeptidase‐4 (DPP4) as an effective probe for detecting senescent cells through an enzymatic activity‐based screening of fluorescent probes. We also determined that these probes were highly, selectively, and rapidly activated in senescent cells during live cell imaging. Furthermore, we successfully visualized senescent cells in the organs of mice using DPP4‐targeted probes. These results are expected to lead to the development of a diagnostic technology for noninvasively detecting senescent cells in vivo and could play a role in the application of DPP4 prodrugs for senotherapy.