title: Development of targetable two-photon fluorescent probes to image hypochlorous Acid in mitochondria and lysosome in live cell and inflamed mouse model.
abstract: Hypochlorous acid (HOCl), as a highly potent oxidant, is well-known as a key "killer" for pathogens in the innate immune system. Recently, mounting evidence indicates that intracellular HOCl plays additional important roles in regulating inflammation and cellular apoptosis. However, the organelle(s) involved in the distribution of HOCl remain unknown, causing difficulty to fully exploit its biological functions in cellular signaling pathways and various diseases. One of the main reasons lies in the lack of effective chemical tools to directly detect HOCl at subcellular levels due to low concentration, strong oxidization, and short lifetime of HOCl. Herein, the first two-photon fluorescent HOCl probe (TP-HOCl 1) and its mitochondria- (MITO-TP) and lysosome- (LYSO-TP) targetable derivatives for imaging mitochondrial and lysosomal HOCl were reported. These probes exhibit fast response (within seconds), good selectivity, and high sensitivity (<20 nM) toward HOCl. In live cell experiments, both probes MITO-TP and LYSO-TP were successfully applied to detect intracellular HOCl in corresponding organelles. In particular, the two-photon imaging of MITO-TP and LYSO-TP in murine model shows that higher amount of HOCl can be detected in both lysosome and mitochondria of macrophage cells during inflammation condition. Thus, these probes could not only help clarify the distribution of subcellular HOCl, but also serve as excellent tools to exploit and elucidate functions of HOCl at subcellular levels.
authors.affiliation: †Department of Chemistry, National University of Singapore, Singapore 117543.|‡State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: Yuan
authors.affiliation: †Department of Chemistry, National University of Singapore, Singapore 117543.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.affiliation: †Department of Chemistry, National University of Singapore, Singapore 117543.
authors.forename: Bikram Keshari
authors.initials: BK
authors.lastname: Agrawalla
authors.affiliation: §Laboratory of Bioimaging Probe Development, Singapore Bioimaging Consortium, Singapore 117543.
authors.forename: Sung-Jin
authors.initials: SJ
authors.lastname: Park
authors.affiliation: †Department of Chemistry, National University of Singapore, Singapore 117543.
authors.forename: Hai
authors.initials: H
authors.lastname: Zhu
authors.affiliation: §Laboratory of Bioimaging Probe Development, Singapore Bioimaging Consortium, Singapore 117543.
authors.forename: Balasubramaniam
authors.initials: B
authors.lastname: Sivaraman
authors.affiliation: §Laboratory of Bioimaging Probe Development, Singapore Bioimaging Consortium, Singapore 117543.
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Peng
authors.affiliation: †Department of Chemistry, National University of Singapore, Singapore 117543.
authors.forename: Qing-Hua
authors.initials: QH
authors.lastname: Xu
authors.affiliation: †Department of Chemistry, National University of Singapore, Singapore 117543.|§Laboratory of Bioimaging Probe Development, Singapore Bioimaging Consortium, Singapore 117543.
authors.forename: Young-Tae
authors.initials: YT
authors.lastname: Chang
mesh_terms: D000818:Animals; D002470:Cell Survival; D004195:Disease Models, Animal; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D006997:Hypochlorous Acid / Q000032:analysis* / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism / Q000473:pathology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008247:Lysosomes / Q000737:chemistry* / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000737:chemistry* / Q000378:metabolism; D015394:Molecular Structure; D017785:Photons; D013050:Spectrometry, Fluorescence
chemical_list: D005456:Fluorescent Dyes; D008070:Lipopolysaccharides; D006997:Hypochlorous Acid