title: Oxazine conjugated nanoparticle detects in vivo hypochlorous acid and peroxynitrite generation.
abstract: 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 approximately 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.
authors.affiliation: Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, 185 Cambridge St., Boston, Massachusetts 02114, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Panizzi
authors.forename: Matthias
authors.initials: M
authors.lastname: Nahrendorf
authors.forename: Moritz
authors.initials: M
authors.lastname: Wildgruber
authors.forename: Peter
authors.initials: P
authors.lastname: Waterman
authors.forename: Jose-Luiz
authors.initials: JL
authors.lastname: Figueiredo
authors.forename: Elena
authors.initials: E
authors.lastname: Aikawa
authors.forename: Jason
authors.initials: J
authors.lastname: McCarthy
authors.forename: Ralph
authors.initials: R
authors.lastname: Weissleder
authors.forename: Scott A
authors.initials: SA
authors.lastname: Hilderbrand
mesh_terms: D000818:Animals; D006997:Hypochlorous Acid / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000378:metabolism; D053758:Nanoparticles; D010078:Oxazines / Q000737:chemistry* / Q000493:pharmacokinetics; D030421:Peroxynitrous Acid / Q000096:biosynthesis*; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D010078:Oxazines; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D030421:Peroxynitrous Acid; D006997:Hypochlorous Acid