溶酶体
化学
组织蛋白酶B
组织蛋白酶D
组织蛋白酶
荧光寿命成像显微镜
荧光
癌细胞
蛋白酶
细胞生物学
生物化学
癌症
酶
内科学
生物
物理
医学
量子力学
作者
Yuqi Wang,Jinbo Li,Liandong Feng,Jingfang Yu,Yan Zhang,Deju Ye,Hong‐Yuan Chen
出处
期刊:Analytical Chemistry
[American Chemical Society]
日期:2016-11-30
卷期号:88 (24): 12403-12410
被引量:80
标识
DOI:10.1021/acs.analchem.6b03717
摘要
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.
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