ABSTRACT
Cellular senescence, a process that arrests the cell cycle, is a cellular response mechanism for various stresses and is implicated in aging and various age-related diseases. However, the understanding of senescence in living organisms is insufficient, largely due to the scarcity of sensitive tools for the detection of cellular senescence in vivo. Herein, we describe the development of a self-immobilizing near-infrared (NIR) fluorogenic probe that can be activated by senescence-associated ß-galactosidase (SA-ß-Gal), the most widely used senescence marker. The NIR signal is turned on only in the presence of SA-ß-Gal, and the fluorescence signal is retained to the site of activation via in situ labeling, significantly enhancing the sensitivity of the probe. We demonstrate its efficient noninvasive imaging of senescence in mice xenograft models.
Subject(s)
Cellular Senescence , Fluorescent Dyes/chemistry , Spectroscopy, Near-Infrared/methods , Animals , Computer Simulation , Heterografts , Mice , beta-Galactosidase/chemistryABSTRACT
Detection of cellular senescence is important not only in the study of senescence in various biological systems, but also in various practical applications such as image-guided surgical removal of senescent cells, as well as the monitoring of drug-responsiveness during cancer therapies. Due to the lack of suitable imaging probes for senescence detection, particularly in living subjects, we have developed an activatable near-infrared (NIR) molecular probe with far-red excitation, NIR emission, and high "turn-on" ratio upon senescence-associated ß-galactosidase (SABG) activation. We present here the first successful demonstration of NIR imaging of DNA damage-induced senescence both in vitro and in human tumor xenograft models.
