A renal clearable fluorogenic probe for in vivo detection of cellular senescence

Abstract

There is a growing need for non-invasive, cheap, and versatile diagnostic methods and the development of low-cost point-of-care assays constitutes a potential solution. Here, we describe the design of a renal clearable fluorogenic probe (Cy7Gal) which produces a fluorogenic signal readable in the urine. The Cy7Gal probe is applied to the detection of the burden of senescence in several in vivo models. The probe is composed of a dye (Cy7) conjugated with a galactose derivative. Upon administration of the probe in vivo, the up-regulated β-galactosidase enzyme in senescent cells cleaves the O-glycosidic bond in Cy7Gal, releasing the highly emissive Cy7 dye that is renally cleared and measured in unmodified urine by an IVIS imaging system or by a fluorimeter. A good correlation between the burden of senescence and emission in urine is observed. Cy7Gal probe is the first example for the fluorogenic in vivo detection of senescence in urine and may serve as a basis for the development of generalized fluorogenic diagnostic platforms for the easy diagnosis in the urine of different diseases as well as for monitoring therapeutic treatments without the use of expensive equipment or trained personnel.

Pharmacological Senolysis as a New Therapeutic Approach for the Prevention of Doxorubicin-Induced Cardiotoxicity

“…In this regard, our group has previously designed different molecular probes to detect cellular senescence in mice bearing tumor xenografts. Further studies in this field would be crucial for monitoring different senescence-related diseases as well as senolytic therapy (Lozano-Torres et al, 2017Lozano-Torres, Blandez, et al, 2021;Lozano-Torres, Rojas-Vázquez, et al, 2021).…”