Journal
ADVANCED MATERIALS
Volume 34, Issue 3, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adma.202107444
Keywords
aggregation-induced emission; cell penetrating peptides; fluorescent probes; pancreatic cancer diagnosis
Categories
Funding
- National Key Research and Development Program [SQ2021YFA090164]
- NSFC Science Center Program [21788102]
- NSFC/China [91959202, 21974047, 21622602]
- Pujiang Talents Plan [19PJ1402300]
- China Postdoctoral Science Foundation [2020M671328]
- Postdoctoral Science Foundation of Jiangsu Province [2020Z189]
- Shanghai Municipal Science and Technology Major Project [2018SHZDZX03]
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In this study, an enzyme-activated aggregation-induced-emission (AIE) probe for high-contrast fluorescence diagnosis of pancreatic cancer (PC) was developed by monitoring the specific overexpressed enzyme Cathepsin E (CTSE). The probe successfully achieved intraoperative diagnosis and tracking of PC in living animal models, addressing accuracy and penetration issues simultaneously. This strategy can expand the database of biocompatible AIE-active probes, especially for establishing intraoperative pathological fluorescent diagnosis.
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.
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