Precise diagnosis of pancreatic fibrosis using fluorescent aptamer probes targeting cellular fibronectin

Pancreatic fibrosis represents a progressive and pathological hallmark of chronic pancreatitis and serves as a valuable diagnostic marker for pancreatic diseases, including pancreatic cancer. However, early detection and accurate staging of pancreatic fibrosis remain significant clinical challenges. Extracellular matrix molecules, particularly fibronectin, have emerged as promising biomarkers for advanced diagnostic imaging. In this study, we introduce a novel approach utilizing DNA aptamer ZY-1-based fluorescent probes, specifically designed to target cellular fibronectin, as an innovative tool for the early detection and precise staging of pancreatic fibrosis. We first demonstrated the exceptional specificity and sensitivity of ZY-1 in binding cellular fibronectin on activated mouse pancreatic stellate cells. Building on this, we conducted comprehensive evaluations of the real-time imaging capabilities of ZY-1 fluorescent probes in mouse models, successfully distinguishing pancreatic fibrosis across different developmental stages. Furthermore, we rigorously validated the diagnostic potential of these probes using biopsy samples from patients with varying degrees of pancreatic fibrosis. This study represents the first systematic application of ZY-1 fluorescent probes for identifying and discriminating mild, intermediate, and severe pancreatic fibrosis in both experimental animal models and human clinical specimens. Our findings provide a critical foundation for advancing clinical diagnosis and personalized treatment strategies for pancreatic fibrosis-related pathologies. STATEMENT OF SIGNIFICANCE: Pancreatic fibrosis marks chronic pancreatitis and helps diagnose diseases such as pancreatic cancer, yet early detection and staging remain clinical challenges. Building on our prior work with the DNA aptamer ZY-1 targeting cellular fibronectin (cFN) for early liver fibrosis, we extend ZY-1 to pancreatic fibrosis, an underexplored disease. We demonstrate strong binding specificity and sensitivity of ZY-1 to activated pancreatic stellate cells and validate detection across Caerulein-induced mouse models and human biopsy samples at multiple stages. This work delivers a novel, noninvasive molecular imaging tool with stage-specific detection, broadening ZY-1's translational potential and addressing the urgent need for improved pancreatic fibrosis diagnostics.