An Enzyme-Activatable Aggregation-Induced-Emission Probe: Intraoperative Pathological Fluorescent Diagnosis of Pancreatic Cancer via Specific Cathepsin E.
Zhirong ZhuQi WangXiaoyan ChenQuan WangChengxu YanXiaolei ZhaoWeijun ZhaoWei-Hong ZhuPublished in: Advanced materials (Deerfield Beach, Fla.) (2021)
Pancreatic cancer (PC) is one of the most devastating malignant tumors. However, fluorescence probes for early clinical diagnosis of PC often encounter difficulties in accuracy and penetrability. In this work, an enzyme-activated aggregation-induced-emission (AIE) probe, QM-HSP-CPP, for high-contrast fluorescence diagnosis of PC is developed by monitoring specific overexpressed enzyme Cathepsin E (CTSE). The probe is composed of an AIE fluorophore QM-COOH (QM = quinoline-malononitrile), CTSE-triggered hydrophobic peptide (HSP), and hydrophilic biocompatible cell penetrating peptide (CPP). The CPP unit can well-modulate the molecular dispersion properties, giving initial fluorescence-off state in the aqueous biosystem, thus endowing high signal-to-noise ratio, and finally overcoming the poor targeting selectivity of traditional AIE probes. CPP can ensure cell/tissue penetrating ability, thus allowing on-site monitoring of endogenous CTSE in PC cells, tissues, and living animal models. When the QM-HSP-CPP probe is specifically cleaved by CTSE, it can generate AIE signals in situ with high-specificity and long-term tracking ability, and successfully achieve intraoperative diagnosis of human PC sections, tracking PC in heterotopic nude mice models. The CTSE-enzyme-triggered AIEgens' liberation strategy improves accuracy and addresses the penetration problem simultaneously, which can expand the database of multitudinous biocompatible AIE-active probes, especially for establishing intraoperative pathological fluorescent diagnosis.
Keyphrases
- living cells
- fluorescent probe
- single molecule
- heat shock protein
- quantum dots
- single cell
- ionic liquid
- small molecule
- gene expression
- heat stress
- magnetic resonance
- emergency department
- endothelial cells
- cell therapy
- heat shock
- magnetic resonance imaging
- type diabetes
- stem cells
- mass spectrometry
- air pollution
- bone marrow
- electronic health record