title: A Lysosome-Targeting Fluorescence Off-On Probe for Imaging of Nitroreductase and Hypoxia in Live Cells.
abstract: A lysosome-targeting fluorescent off-on probe has been developed by one-step synthesis for detecting lysosomal nitroreductase and hypoxia. The probe is constructed by incorporating morpholine (a lysosome-targeting unit) into 4-nitro-1,8-naphthalimide (as a fluorochrome and specific substrate for nitroreductase), and the detection mechanism is based on the nitroreductase-catalyzed reduction of the probe to 4-amino-1,8-naphthalimide, accompanied by a large fluorescence enhancement at a wavelength of 543 nm. The probe shows an accurate lysosome-targeting ability with high selectivity and sensitivity to nitroreductase (detection limit: 2.2 ng mL-1). Notably, the probe has been used to image the change of lysosomal nitroreductase in live cells during hypoxia, revealing that the increase of nitroreductase in lysosomes may be smaller than that in the cytoplasm. In addition, the probe is expected to be useful for studying the function of nitroreductase in the acidic organelle of lysosomes.
authors: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.
authors: Jin
authors: J
authors: Zhou
authors: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.
authors: Wen
authors: W
authors: Shi
authors: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.
authors: Li-Hong
authors: LH
authors: Li
authors: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.
authors: Qiu-Yu
authors: QY
authors: Gong
authors: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.
authors: Xiao-Feng
authors: XF
authors: Wu
authors: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.
authors: Xiao-Hua
authors: XH
authors: Li
authors: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China. mahm@iccas.ac.cn.
authors: Hui-Min
authors: HM
authors: Ma
mesh_terms: D015057:1-Naphthylamine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D000072283:A549 Cells; D055162:Biocatalysis; D002470:Cell Survival / Q000187:drug effects; D003287:Contrast Media / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D005456:Fluorescent Dyes / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008247:Lysosomes / Q000737:chemistry* / Q000378:metabolism; D008856:Microscopy, Fluorescence; D053644:Naphthalimides / Q000737:chemistry* / Q000378:metabolism; D009601:Nitroreductases / Q000737:chemistry / Q000378:metabolism*; D015363:Quinolones / Q000737:chemistry* / Q000378:metabolism; D013696:Temperature; D000072258:Tumor Hypoxia
chemical_list: D003287:Contrast Media; D005456:Fluorescent Dyes; D053644:Naphthalimides; D015363:Quinolones; C086538:4-amino-1,8-naphthalimide; D015057:1-Naphthylamine; D009601:Nitroreductases
keywords: cell hypoxia; fluorescence imaging; fluorescent probes; imaging agents; lysosome; nitroreductase