title: Two-photon dual imaging platform for in vivo monitoring cellular oxidative stress in liver injury.
abstract: Oxidative stress reflects an imbalance between reactive oxygen species (ROS) and antioxidants, which has been reported as an early unifying event in the development and progression of various diseases and as a direct and mechanistic indicator of treatment response. However, highly reactive and short-lived nature of ROS and antioxidant limited conventional detection agents, which are influenced by many interfering factors. Here, we present a two-photon sensing platform for in vivo dual imaging of oxidative stress at the single cell-level resolution. This sensing platform consists of three probes, which combine the turn-on fluorescent transition-metal complex with different specific responsive groups for glutathione (GSH), hydrogen peroxide (H2O2) and hypochlorous acid (HOCl). By combining fluorescence intensity imaging and fluorescence lifetime imaging, these probes totally remove any possibility of crosstalk from in vivo environmental or instrumental factors, and enable accurate localization and measurement of the changes in ROS and GSH within the liver. This precedes changes in conventional biochemical and histological assessments in two distinct experimental murine models of liver injury. The ability to monitor real-time cellular oxidative stress with dual-modality imaging has significant implications for high-accurate, spatially configured and quantitative assessment of metabolic status and drug response.
authors.affiliation: Therapeutics Research Centre, School of Medicine, The University of Queensland, Princess Alexandra Hospital, Woolloongabba, QLD 4102, Australia.|Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 1630 S. Dongfang Road, Shanghai, 200127, China.
authors.forename: Haolu
authors.initials: H
authors.lastname: Wang
authors.affiliation: Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St Lucia, QLD 4072, Australia.
authors.forename: Run
authors.initials: R
authors.lastname: Zhang
authors.affiliation: School of Medicine, The University of Queensland, Gallipoli Medical Research Institute, Greenslopes Private Hospital, Greenslopes, QLD 4120, Australia.
authors.forename: Kim R
authors.initials: KR
authors.lastname: Bridle
authors.affiliation: School of Medicine, The University of Queensland, Gallipoli Medical Research Institute, Greenslopes Private Hospital, Greenslopes, QLD 4120, Australia.
authors.forename: Aparna
authors.initials: A
authors.lastname: Jayachandran
authors.affiliation: Department of Gastroenterology, The Prince Charles Hospital, School of Medicine, The University of Queensland, Chermside, QLD 4032, Australia.
authors.forename: James A
authors.initials: JA
authors.lastname: Thomas
authors.affiliation: State Key Laboratory of Fine Chemicals, School of Chemistry, Dalian University of Technology, Dalian, 116024, China.
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, China.
authors.forename: Jingli
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St Lucia, QLD 4072, Australia.
authors.forename: Zhi Ping
authors.initials: ZP
authors.lastname: Xu
authors.affiliation: School of Medicine, The University of Queensland, Gallipoli Medical Research Institute, Greenslopes Private Hospital, Greenslopes, QLD 4120, Australia.
authors.forename: Darrell H G
authors.initials: DH
authors.lastname: Crawford
authors.affiliation: Therapeutics Research Centre, School of Medicine, The University of Queensland, Princess Alexandra Hospital, Woolloongabba, QLD 4102, Australia.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Liang
authors.affiliation: Therapeutics Research Centre, School of Medicine, The University of Queensland, Princess Alexandra Hospital, Woolloongabba, QLD 4102, Australia.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Therapeutics Research Centre, School of Medicine, The University of Queensland, Princess Alexandra Hospital, Woolloongabba, QLD 4102, Australia.|School of Pharmacy and Medical Science, University of South Australia, Adelaide, SA 5001, Australia.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Roberts
mesh_terms: D000082:Acetaminophen / Q000633:toxicity; D000818:Animals; D002460:Cell Line; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism / Q000473:pathology*; D056831:Coordination Complexes / Q000737:chemistry; D004195:Disease Models, Animal; D005456:Fluorescent Dyes / Q000737:chemistry*; D005978:Glutathione / Q000737:chemistry / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000737:chemistry / Q000378:metabolism; D006997:Hypochlorous Acid / Q000737:chemistry; D008099:Liver / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D036641:Microscopy, Fluorescence, Multiphoton; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000737:chemistry / Q000378:metabolism; D012428:Ruthenium / Q000737:chemistry
chemical_list: D056831:Coordination Complexes; D005456:Fluorescent Dyes; D017382:Reactive Oxygen Species; D000082:Acetaminophen; D006997:Hypochlorous Acid; D012428:Ruthenium; D006861:Hydrogen Peroxide; D005978:Glutathione