Two-photon dual imaging platform for in vivo monitoring cellular oxidative stress in liver injury

Haolu Wang; Run Zhang; Kim R. Bridle; Aparna Jayachandran; James A. Thomas; Wenzhu Zhang; Jingli Yuan; Zhi Ping Xu; Darrell H.G. Crawford; Xiaowen Liang; Xin Liu; Michael S. Roberts

doi:10.1038/srep45374

Two-photon dual imaging platform for in vivo monitoring cellular oxidative stress in liver injury

Haolu Wang, Run Zhang, Kim R. Bridle, Aparna Jayachandran, James A. Thomas, Wenzhu Zhang, Jingli Yuan, Zhi Ping Xu, Darrell H.G. Crawford, Xiaowen Liang^*, Xin Liu, Michael S. Roberts

^*Corresponding author for this work

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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.

Original language	English
Article number	45374
Pages (from-to)	1-11
Number of pages	11
Journal	Scientific Reports
Volume	7
DOIs	https://doi.org/10.1038/srep45374
Publication status	Published - 28 Mar 2017
Externally published	Yes

Bibliographical note

Copyright the Author(s) 2017. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

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10.1038/srep45374

Publisher Version (open access)Final published version, 1.89 MBLicence: CC BY

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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.",

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AU - Wang, Haolu

AU - Zhang, Run

AU - Bridle, Kim R.

AU - Jayachandran, Aparna

AU - Thomas, James A.

AU - Zhang, Wenzhu

AU - Yuan, Jingli

AU - Xu, Zhi Ping

AU - Crawford, Darrell H.G.

AU - Liang, Xiaowen

AU - Liu, Xin

AU - Roberts, Michael S.

N1 - Copyright the Author(s) 2017. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

PY - 2017/3/28

Y1 - 2017/3/28

N2 - 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.

AB - 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.

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Two-photon dual imaging platform for in vivo monitoring cellular oxidative stress in liver injury

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