title: Lysosome-Targeting Fluorogenic Probe for Cathepsin B Imaging in Living Cells.
abstract: 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.
authors.affiliation: State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing, 210023, China.
authors.forename: Yuqi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing, 210023, China.
authors.forename: Jinbo
authors.initials: J
authors.lastname: Li
authors.affiliation: State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing, 210023, China.
authors.forename: Liandong
authors.initials: L
authors.lastname: Feng
authors.affiliation: State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing, 210023, China.
authors.forename: Jingfang
authors.initials: J
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing, 210023, China.
authors.forename: Yan
authors.identifier: 0000-0002-8858-8894
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing, 210023, China.
authors.forename: Deju
authors.identifier: 0000-0002-9887-0914
authors.initials: D
authors.lastname: Ye
authors.affiliation: State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing, 210023, China.
authors.forename: Hong-Yuan
authors.initials: HY
authors.lastname: Chen
mesh_terms: D001592:Benzyl Alcohols / Q000737:chemistry; D002401:Cathepsin B / Q000032:analysis*; D045744:Cell Line, Tumor; D005453:Fluorescence; D005456:Fluorescent Dyes / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D008247:Lysosomes / Q000737:chemistry* / Q000473:pathology; D008856:Microscopy, Fluorescence / Q000379:methods; D009369:Neoplasms / Q000737:chemistry / Q000473:pathology; D009842:Oligopeptides / Q000737:chemistry*; D061848:Optical Imaging / Q000379:methods
chemical_list: D001592:Benzyl Alcohols; D005456:Fluorescent Dyes; D009842:Oligopeptides; C006503:4-aminobenzyl alcohol; D002401:Cathepsin B