A new class of fast-response and highly selective fluorescent probes for visualizing peroxynitrite in live cells, subcellular organelles, and kidney tissue of diabetic rats

Publication date: November 2016
Source:Biomaterials, Volume 107
Author(s): Junfeng Miao, Yingying Huo, Qian Liu, Zhe Li, Heping Shi, Yawei Shi, Wei Guo
Peroxynitrite (ONOO⁻) is an extremely powerful oxidant in biological systems, and can react with a wide variety of molecular targets including proteins, lipids, and nucleic acids, eventually resulting in a series of disease states such as diabetes, Alzheimer's disease, cancer, arthritis, autoimmune, and other disorders. In this work, we present a new class of ONOO⁻ fluorescent probes by exploiting the ONOO⁻-triggered N-oxidation and N-nitrosation reactions of aromatic tertiary amine for the first time. The as-obtained fluorescent probe A2 could detect ONOO⁻ with quite fast fluorescence off-on response (within seconds), ultrasensitivity (detection limit: <2 nM), and excellent selectivity over a series of biologically relevant reactive oxygen species as well as metal cations. With the probe, the endogenous ONOO⁻ in activated RAW264.7 murine macrophage, EA.hy926 endothelial cells after oxygen glucose deprivation and reoxygenation (OGD/RO), and kidney tissue of diabetic rats has been successfully visualized. Based on the molecular platform of A2, we further develop its mitochondria- and lysosome-targetable fluorescent probes Mito-A2 and Lyso-A2 by installing the corresponding targeting groups to alkoxy unit of A2, and confirm their abilities to image ONOO⁻ in mitochondria and lysosomes, respectively, by co-localization assays. It is greatly expected that these probes can serve as useful imaging tools for clarifying the distribution and pathophysiological functions of ONOO⁻ in cells, subcellular organelles, and animal tissues.

Graphical abstract

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