Activatable Molecular Imaging Probe Targeting Pancreatic Lipase for Early Diagnosis of Pancreatic Diseases

Abstract

Acute pancreatitis involves the abnormal activation of pancreatic enzymes triggered by diverse pathological factors, resulting in tissue edema, autodigestion, hemorrhage, necrosis, systemic inflammation, and potentially, multi-organ failure. Pancreatic lipase (PL) plays a central role in this cascade, initiating pancreatic autodigestion at the early stages of the disease. Leveraging this pathophysiological hallmark, we developed a novel near-infrared (NIR) fluorescent probe, NRO-PL, using 9-(diethylamino)-2-hydroxy-5H-benzo[a]phenoxazin-5-one as the fluorophore and lauroyl chloride as the PL-responsive moiety. Synthesized via a straightforward protocol, the probe had high sensitivity toward PL (limit of detection=2.9 mU/mL) and was successfully employed in real-time visualization of enzyme activity. In vitro studies demonstrated that the probe could accurately track the dynamics of PL in cell models of pancreatitis. In vivo imaging in murine models revealed the probe’s strong contrast and specificity for inflamed pancreatic tissues. This probe is a valuable molecular tool for real-time monitoring of PL activity. It can be employed to provide new insights into the enzyme mechanisms underlying the progression of pancreatitis.

Keywords

Pancreatic lipase (PL) / Fluorescent probe / Turn-on response / Pancreatitis imaging

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Jilin University, The Editorial Department of Chemical Research in Chinese Universities and Springer-Verlag GmbH