A Renal Clearable Probe for In Vivo Monoamine Oxidase (MAO) Detection.

Abstract

Hyperactivation of monoamine oxidase enzymes (MAO) is associated with uncontrolled production of neurotoxic compounds such as reactive oxygen species, whose accumulation is linked to neurodegenerative, chronic, and age-related diseases. Although chromo-fluorogenic probes for detecting and quantifying MAO activity have been reported, non-invasive methods for monitoring MAO overexpression in vivo remain elusive. Here, we report a renal-clearable fluorogenic probe based on the cyanine-7 fluorophore (Cy7-MAO) for in vivo detection of MAO overexpression through a simple measurement of the fluorescence in urine. The probe incorporates sulfonic acid moieties for renal clearance and a propylamino group as a MAO substrate. Upon administration, Cy7-MAO is hydrolysed at the site by MAO, releasing a highly emissive Cy7 fluorophore, which is excreted in urine and quantified by fluorescence. Cy7-MAO is validated in vitro using HepG2 liver human cells, which express elevated MAO levels. We further demonstrate the in vivo applicability of Cy7-MAO for MAO activity monitoring in aged mice, which show significantly higher urine fluorescence than young mice, consistent with an elevated MAO activity in older animals. These findings support Cy7-MAO as a tool for longitudinal assessment of MAO activity in vivo, providing a novel approach to study MAO-related pathologies.