title: A ruthenium(II) complex-based lysosome-targetable multisignal chemosensor for in vivo detection of hypochlorous acid.
abstract: Although considerable efforts have been made for the development of ruthenium(II) complex-based chemosensors and bioimaging reagents, the multisignal chemosensor using ruthenium(II) complexes as the reporter is scarce. In addition, the mechanisms of cellular uptake of ruthenium(II)-based chemosensors and their intracellular distribution are ill-defined. Herein, a new ruthenium(II) complex-based multisignal chemosensor, Ru-Fc, is reported for the highly sensitive and selective detection of lysosomal hypochlorous acid (HOCl). Ru-Fc is weakly luminescent because the MLCT (metal-to-ligand charge transfer) state is corrupted by the efficient PET (photoinduced electron transfer) process from Fc (ferrocene) moiety to Ru(II) center. The cleavage of Fc moiety by a HOCl-induced specific reaction leads to elimination of PET, which re-establishes the MLCT state of the Ru(II) complex, accompanied by remarkable photoluminescence (PL) and electrochemiluminescence (ECL) enhancements. The result of MTT assay showed that the proposed chemosensor, Ru-Fc, was low cytotoxicity. The applicability of Ru-Fc for the quantitative detection of HOCl in live cells was demonstrated by the confocal microscopy imaging and flow cytometry analysis. Dye colocalization studies confirmed very precise distribution of the Ru(II) complex in lysosomes, and inhibition studies revealed that the caveolae-mediated endocytosis played an important role during the cellular internalization of Ru-Fc. By using Ru-Fc as a chemosensor, the imaging of the endogenous HOCl generated in live macrophage cells during the stimulation was achieved. Furthermore, the practical applicability of Ru-Fc was demonstrated by the visualizing of HOCl in laboratory model animals, Daphnia magna and zebrafish.
authors.affiliation: State Key Laboratory of Fine Chemicals, School of Chemistry, Dalian University of Technology, Dalian 116024, PR China.
authors.forename: Liyan
authors.initials: L
authors.lastname: Cao
authors.affiliation: State Key Laboratory of Fine Chemicals, School of Chemistry, Dalian University of Technology, Dalian 116024, PR China.
authors.forename: Run
authors.initials: R
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Fine Chemicals, School of Chemistry, Dalian University of Technology, Dalian 116024, PR China. Electronic address: wzhzhang@dlut.edu.cn.
authors.forename: Wenzhu
authors.initials: W
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Fine Chemicals, School of Chemistry, Dalian University of Technology, Dalian 116024, PR China.
authors.forename: Zhongbo
authors.initials: Z
authors.lastname: Du
authors.affiliation: State Key Laboratory of Fine Chemicals, School of Chemistry, Dalian University of Technology, Dalian 116024, PR China.
authors.forename: Chunjun
authors.initials: C
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Fine Chemicals, School of Chemistry, Dalian University of Technology, Dalian 116024, PR China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Ye
authors.affiliation: State Key Laboratory of Fine Chemicals, School of Chemistry, Dalian University of Technology, Dalian 116024, PR China.
authors.forename: Bo
authors.initials: B
authors.lastname: Song
authors.affiliation: State Key Laboratory of Fine Chemicals, School of Chemistry, Dalian University of Technology, Dalian 116024, PR China. Electronic address: jlyuan@dlut.edu.cn.
authors.forename: Jingli
authors.initials: J
authors.lastname: Yuan
mesh_terms: D000818:Animals; D015374:Biosensing Techniques / Q000295:instrumentation*; D003621:Daphnia; D004867:Equipment Design; D019544:Equipment Failure Analysis; D006997:Hypochlorous Acid / Q000378:metabolism*; D008163:Luminescent Measurements / Q000295:instrumentation*; D008247:Lysosomes / Q000378:metabolism*; D015203:Reproducibility of Results; D012428:Ruthenium / Q000737:chemistry*; D012680:Sensitivity and Specificity; D015027:Zebrafish
chemical_list: D006997:Hypochlorous Acid; D012428:Ruthenium
keywords: Bioimaging; Hypochlorous acid; In vivo analysis; Multisignal chemosensor; Ruthenium(II) complex