Renal-clearable fluorescent probe for early detection of pancreatic cancer in living murine models

Pancreatic cancer (PC) is a highly aggressive and lethal malignancy with extremely poor patient survival rates. The lack of biomarkers and deep tissue detection barriers has presented long-standing and unsolved issues, severely hindering the early diagnosis of PC even in living rodent models. Here, we report a renal-clearable leucine aminopeptidase (LAP)–activatable fluorescence probe, overturning the probe’s pharmacokinetics from the liver to kidney pathway (90% of the injection dosage). This strategy reduces interference in the liver and enables LAP as a biomarker for PC detection in murine models. After in situ response with LAP in the pancreas, renal-clearable fluorogenic fragments could be efficiently excreted into the urine, thus addressing the depth barriers of PC. Our strategy has resolved the lack of biomarkers and deep tissue detection barriers in early PC detection in murine models, which would greatly expand the bioanalytical toolbox for PC identification, further enabling the efficient screening of PC drugs at the animal level and the exploration of diagnostic methods for PC.