Activatable optical probe for non-invasive detection of APN activity in diabetes and its complications

Abstract

Background

Diabetes is a major global health issue, primarily characterized by chronic hyperglycemia, and can lead to severe complications such as ovarian dysfunction. Early and accurate diagnosis is critical for effective disease management and prevention of long-term complications. This study explores the clinical potential of Hcy-APN, a diagnostic probe designed to detect aminopeptidase N (APN) activity in solution, cells, and in vivo.

Results

The Hcy-APN probe incorporates a hemicyanine moiety, remaining non-fluorescent until cleaved by APN, which enhances both fluorescence and photoacoustic (PA) signals. In vitro experiments demonstrated a strong correlation between APN concentration and PA intensity, with minimal interference from other bioenzymes. The probe exhibited high stability and consistent PA signals, enabling deep tissue imaging at depths up to 0.6 cm. Cellular imaging confirmed its low cytotoxicity, while in vivo studies in diabetic mice highlighted its effectiveness in monitoring APN activity. Additionally, fluorescence assays of human clinical samples revealed significantly higher signals in serum from patients with ovarian dysfunction, suggesting the probe's diagnostic utility in diabetes-related ovarian conditions.

Significance

This study underscores the potential of Hcy-APN as a valuable tool for clinical diagnostics, particularly in monitoring diabetes-associated complications like ovarian dysfunction. The probe's dual-modality imaging capability (fluorescence and PA) enhances its applicability in deep tissue analysis. Further research is needed to optimize its clinical use and validate its efficacy in improving patient outcomes.