Abstract |
Accumulating evidence suggests that formation of peroxynitrite (ONOO(-)) in the cerebral vasculature contributes to the progression of ischemic damage, while the underlying molecular mechanisms remain elusive. To fully understand ONOO(-) biology, efficient tools that can realize the real-time tracing of endogenous ONOO(-) fluxes are indispensable. While a few ONOO(-) fluorescent probes have been reported, direct visualization of ONOO(-) fluxes in the cerebral vasculature of live mice remains a challenge. Herein, we present a fluorescent switch-on probe (NP3) for ONOO(-) imaging. NP3 exhibits good specificity, fast response, and high sensitivity toward ONOO(-) both in vitro and in vivo. Moreover, NP3 is two-photon excitable and readily blood-brain barrier penetrable. These desired photophysical and pharmacokinetic properties endow NP3 with the capability to monitor brain vascular ONOO(-) generation after injury with excellent temporal and spatial resolution. As a proof of concept, NP3 has enabled the direct visualization of neurovascular ONOO(-) formation in ischemia progression in live mouse brain by use of two-photon laser scanning microscopy. Due to these favorable properties, NP3 holds great promise for visualizing endogenous peroxynitrite fluxes in a variety of pathophysiological progressions in vitro and in vivo.
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Authors | Xin Li, Rong-Rong Tao, Ling-Juan Hong, Juan Cheng, Quan Jiang, Ying-Mei Lu, Mei-Hua Liao, Wei-Feng Ye, Nan-Nan Lu, Feng Han, Yong-Zhou Hu, You-Hong Hu |
Journal | Journal of the American Chemical Society
(J Am Chem Soc)
Vol. 137
Issue 38
Pg. 12296-303
(Sep 30 2015)
ISSN: 1520-5126 [Electronic] United States |
PMID | 26352914
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Fluorescent Dyes
- Peroxynitrous Acid
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Topics |
- Animals
- Cerebrovascular Trauma
(metabolism, pathology)
- Endothelial Cells
(chemistry, metabolism)
- Fluorescent Dyes
(chemical synthesis, chemistry, pharmacokinetics)
- Mice
- Molecular Structure
- Peroxynitrous Acid
(chemistry, metabolism)
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