Enzyme-Activatable Aggregation-Induced Emission Probe: Intraoperative-Pathological Fluorescent Diagnosis of Pancreatic Cancer via Specific Cathepsin E.

Pancreatic cancer (PC) is one of the most devastating malignant tumors. However, fluorescence probes for early clinical diagnosis of PC often encounter difficulties in the accuracy and penetrability. Herein, we develop an enzyme activatied aggregation-induced emission (AIE) probe QM-HSP-CPP for high-contrast fluorescence diagnosis of PC by monitoring specific overexpressed enzyme Cathepsin E (CTSE). The probe is composed of an AIE fluorophore QM-COOH, CTSE-triggered hydrophobic peptide (HSP), and hydrophilic biocompatible cell penetrating peptide (CPP). The CPP unit could well modulate the molecular dispersion properties, giving the initial fluorescence-off state in the aqueous biosystem, thus endowing high signal-to-noise ratio, and finially overcoming the poor targeting selectivity of traditional AIE probes. CPP can ensure cell/tissue penetrating ability, thus allowing on-site monitoring endogenous CTSE in PC cells, tissues, and living animal models. When the probe QM-HSP-CPP is specifically cleaved by CTSE, it could generate AIE signals in situ with high-specificity and long-term tracking ability, and successfully achieve the intraoperatively diagnosis of human PC sections and tracking PC in heterotopic nude mice models. The CTSE enzyme-triggered AIEgens liberation strategy improves the accuracy and addresses the penetration problem simultaneously, which can expand the database of multitudinous biocompatible AIE-active probes, especially for establishing the intraoperative-pathological fluorescent diagnosis. This article is protected by copyright. All rights reserved.