Dual-Parameter Recognition-Directed Design of the Activatable Fluorescence Probe for Precise Imaging of Cellular Senescence
Jili Li, Linlin Wang, Xiyuan Luo, Yinghao Xia, Yuqi Xie, Yanlan Liu, Weihong Tan
Abstract
Specific imaging of cellular senescence emerges as a promising strategy for early diagnosis and treatment of various age-related diseases. The currently available imaging probes are routinely designed by targeting a single senescence-related marker. However, the inherently high heterogeneity of senescence makes them inaccessible to achieve specific and accurate detection of broad-spectrum cellular senescence. Here, we report the design of a dual-parameter recognition fluorescent probe for precise imaging of cellular senescence. This probe remains silent in non-senescent cells, yet produces bright fluorescence after sequential responses to two senescence-associated markers, namely, SA-β-gal and MAO-A. In-depth studies reveal that this probe allows for high-contrast imaging of senescence, independent of the cell source or stress type. More impressively, such dual-parameter recognition design further allows it to distinguish senescence-associated SA-β-gal/MAO-A from cancer-related β-gal/MAO-A, compared to commercial or previous single-marker detection probes. This study offers a valuable molecular tool for imaging cellular senescence, which is expected to significantly expand the basic studies on senescence and facilitate advances of senescence-related disease theranostics.