Oxazine Conjugated Nanoparticle Detects in Vivo Hypochlorous Acid and Peroxynitrite Generation

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• 作者：Peter Panizzi ; Matthias Nahrendorf ; Moritz Wildgruber ; Peter Waterman ; Jose-Luiz Figueiredo ; Elena Aikawa ; Jason McCarthy ; Ralph Weissleder ; Scott A. Hilderbrand
• 刊名：Journal of the American Chemical Society
• 出版年：2009
• 出版时间：November 4, 2009
• 年：2009
• 卷：131
• 期：43
• 页码：15739-15744
• 全文大小：299K
• 年卷期：v.131,no.43(November 4, 2009)
• ISSN：1520-5126

文摘

The current lack of suitable probes has limited the in vivo imaging of reactive oxygen/nitrogen species (ROS/RNS). ROS/RNS are often generated by ischemia-induced inflammation; defining the extent of tissue involvement or ROS/RNS-related damage would have a significant clinical impact. We present the preparation and demonstration of a fluorogenic sensor for monitoring peroxynitrite (ONOO⁻) and myeloperoxidase (MPO) mediated hypochlorous acid (HOCl/OCl⁻) production. The sensor consists of a long circulating biocompatible nanoparticle that targets phagocytic cells in vivo and is coated with 400 quenched oxazine fluorophores that are released by reaction with HOCl or ONOO⁻ but are stable toward oxidants such as hydroxyl radical, hydrogen peroxide, and superoxide. MPO-dependent probe activation is chloride ion dependent and is negated in flow cytometry studies of MPO inhibitor treated neutrophils. Fluorescence reflectance imaging and microscopic fluorescence imaging in mouse hearts after myocardial infarction showed probe release into neutrophil-rich ischemic areas, making this ROS/RNS sensor a novel prognostic indicator.