Sequence-Activated Near-Infrared Fluorescence Probe for Precisely Tracking in Vivo Senescence

Abstract

Real-time monitoring of senescent cells is of great significance for understanding and intervening in aging. Since overexpression of endogenous β-galactosidase (β-gal) is not unique to senescent cells, the probes relying solely on β-gal activity could yield inaccurate senescent cell detection. Herein, we designed a dual-mode sequential response AND logic NIR probe MFB-βgal which contains the β-gal-cleavable unit and morpholine unit serving as an enzymatic activity trigger and a lysosomal targeting moiety. MFB-OH is generated in situ after reaction with β-gal, which can detect the alkalinization of lysosome by emission intensity in senescent cells. This probe has been successfully used to distinguish between SKOV-3 and senescent cells and applied to in vivo visualization of β-gal activity in a mice model, providing a new strategy for the accurate detection of cellular senescence.