Lysosome-Targeting Fluorogenic Probe for Cathepsin B Imaging in Living Cells

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• 作者：Yuqi Wang ; Jinbo Li ; Liandong Feng ; Jingfang Yu ; Yan ZhangDeju Ye ; Hong-Yuan Chen
• 刊名：Analytical Chemistry
• 出版年：2016
• 出版时间：December 20, 2016
• 年：2016
• 卷：88
• 期：24
• 页码：12403-12410
• 全文大小：469K
• ISSN：1520-6882

文摘

Cathepsin B (CTB) is a lysosomal protease which has been recognized as a promising biomarker for many malignant tumors, and accurate detection of its activity is important in early diagnosis of cancers and predicting metastasis. Herein, we reported a lysosome-targeting fluorogenic small-molecule probe for fluorescence imaging of lysosomal CTB in living cancer cells by incorporating a CTB-recognitive peptide substrate Cbz-Lys-Lys-p-aminobenzyl alcohol (Cbz-Lys-Lys-PABA) and a lysosome locating group morpholine. We demonstrated that the probe could be efficiently activated by CTB to generate ∼73-fold enhancement in fluorescence under acidic lysosomal environment (pH 4.5–6.0), allowing for high sensitivity and specificity to detect CTB. Fluorescence imaging results showed selective accumulation and fluorescence turn-on in the lysosomes of cancer cells, which were capable of reporting on lysosomal CTB activity in cancer cells and normal tissue cells. This study highlights the potential of using a lysosome-targeting group to design a sensitive and specific fluorogenic probe for fluorescence imaging of lysosomal CTB in living cells.