Activatable fluorescent probe for auxiliary diagnosis of atherosclerosis: from foam cells to clinical samples

Cardiovascular diseases remain a leading cause of morbidity and mortality worldwide, with atherosclerosis playing a central role in their pathogenesis. A fluorescent probe activatable by leucine aminopeptidase was synthesized and designated as LAP probe. This probe was constructed using a hemicyanine scaffold conjugated with an LAP-recognizing peptide via a condensation reaction. Upon LAP activation, a bathochromic shift in absorption and a marked turn-on fluorescence response in the near-infrared region were observed, with a strong linear correlation established between fluorescence intensity and LAP concentration. The probe successfully distinguished foam cells from normal macrophages and enabled in vivo imaging of atherosclerotic plaques in high-fat diet-fed ApoE-/- mice. Serum LAP activity was found to be significantly elevated in atherosclerotic mice and in patients with arterial stenosis, particularly in those with severe stenosis exceeding 60%, as confirmed by receiver operating characteristic curve analysis. The probe exhibited low toxicity with no observable organ damage. These findings demonstrated that LAP probe holds promise for the auxiliary diagnosis and risk stratification of atherosclerosis.