文献类型：期刊文献

英文题名：An Enzyme-Activatable Aggregation-Induced-Emission Probe: Intraoperative Pathological Fluorescent Diagnosis of Pancreatic Cancer via Specific Cathepsin E

作者：Zhu, Zhirong[1,2];Wang, Qi[1,2];Chen, Xiaoyan[3];Wang, Quan[4];Yan, Chengxu[1,2];Zhao, Xiaolei[1,2];Zhao, Weijun[1,2];Zhu, Wei-Hong[1,2]

机构：[1]East China Univ Sci & Technol, Frontiers Sci Ctr Materiobiol & Dynam Chem, Feringa Nobel Prize Scientist Joint Res Ctr,Key L, Sch Chem & Mol Engn,Shanghai Key Lab Funct Mat Ch, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Frontiers Sci Ctr Materiobiol & Dynam Chem, Feringa Nobel Prize Scientist Joint Res Ctr, Sch Chem & Mol Engn,Inst Fine Chem,Joint Int Res, Shanghai 200237, Peoples R China;[3]Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Dept Pathol, Shanghai 200025, Peoples R China;[4]Shanghai Jiao Tong Univ, Sch Biomed Engn, Renji Hosp, State Key Lab Oncogenes & Related Genes, Shanghai 200030, Peoples R China

年份：2022

卷号：34

期号：3

外文期刊名：ADVANCED MATERIALS

收录：;EI(收录号：20214811242420);WOS:【SCI-EXPANDED(收录号:WOS:000722947500001)】；

基金：This work was supported by the National Key Research and Development Program (SQ2021YFA090164), NSFC Science Center Program (21788102), NSFC/China (91959202, 21974047 and 21622602), Pujiang Talents Plan (19PJ1402300), the China Postdoctoral Science Foundation (2020M671328), the Postdoctoral Science Foundation of Jiangsu Province (2020Z189), and the Shanghai Municipal Science and Technology Major Project (2018SHZDZX03). All of the animal experimental procedures were performed according to the protocols approved by the Animal Care and Use Committee of the Shanghai Cancer Institute. The human tissues were collected by the Ruijin Hospital Affiliated to Shanghai Jiao Tong University School following informed consent, and the study was approved by the ethics board of Ruijin Hospital. The human hepatocyte cell (QSG-7701) and human epithelioid cervical carcinoma cell (HeLa) were purchased from the Institute of Cell Biology (Shanghai, China). Human pancreatic cancer cells (SW1990) were provided by Fudan University. Islet endothelial cells (MS1) were purchased from Fuheng Biology (Shanghai, China).

语种：英文

外文关键词：aggregation-induced emission; cell penetrating peptides; fluorescent probes; pancreatic cancer diagnosis

摘要：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.