title: Theranostic Nucleic Acid Binding Nanoprobe Exerts Anti-inflammatory and Cytoprotective Effects in Ischemic Injury.
abstract: Extracellular nucleic acids are proinflammatory molecules that have been implicated in a diverse range of diseases. We report here the development of a multivalent nucleic acid scavenging nanoprobe, where the fluorochrome thiazole orange (TO) is conjugated to a polymeric 40 kDa dextran carrier. Dextran-TO (Dex-TO) has nanomolar affinity for mammalian and bacterial nucleic acids and attenuates the production of inflammatory cytokines from activated macrophages exposed to DNA and RNA. Mice with myocardial ischemia reperfusion that were treated with Dex-TO showed a decrease in myocardial macrophage infiltration at 24 hours (p<0.05) and a decrease in infarct size (18% ± 9%, p<0.01) on day 7. Dex-TO allows sites of injury to be identified with fluorescence imaging, while simultaneously exerting an anti-inflammatory and cytoprotective effect. Dex-TO could be of significant diagnostic and therapeutic (theranostic) utility in a broad range of conditions including ischemia, trauma, burns, sepsis and autoimmune disease.
authors.affiliation: Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston MA;; Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston MA.
authors.forename: Howard H
authors.initials: HH
authors.lastname: Chen
authors.affiliation: Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston MA (H.C.: currently School of Materials Science and Engineering, Chonnam National University, Gwangju, South Korea).
authors.forename: Hushan
authors.initials: H
authors.lastname: Yuan
authors.affiliation: Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston MA (H.C.: currently School of Materials Science and Engineering, Chonnam National University, Gwangju, South Korea).
authors.forename: Hoonsung
authors.initials: H
authors.lastname: Cho
authors.affiliation: Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston MA (currently Department of Anesthesiology, University of Maryland School of Medicine, Baltimore MD).
authors.forename: Yan
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Division of Genetics and Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston MA.
authors.forename: Soeun
authors.initials: S
authors.lastname: Ngoy
authors.affiliation: Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston MA.
authors.forename: Anand T N
authors.initials: AT
authors.lastname: Kumar
authors.affiliation: Division of Genetics and Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston MA.
authors.forename: Ronglih
authors.initials: R
authors.lastname: Liao
authors.affiliation: Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston MA (currently Department of Anesthesiology, University of Maryland School of Medicine, Baltimore MD).
authors.forename: Wei
authors.initials: W
authors.lastname: Chao
authors.affiliation: Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston MA;; Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston MA (H.C.: currently School of Materials Science and Engineering, Chonnam National University, Gwangju, South Korea).
authors.forename: Lee
authors.initials: L
authors.lastname: Josephson
authors.affiliation: Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston MA;; Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston MA.
authors.forename: David E
authors.initials: DE
authors.lastname: Sosnovik
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D052160:Benzothiazoles / Q000008:administration & dosage; D019610:Cytoprotection; D003911:Dextrans / Q000008:administration & dosage; D051379:Mice; D015428:Myocardial Reperfusion Injury / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D049329:Nanostructures / Q000008:administration & dosage*; D009696:Nucleic Acids / Q000378:metabolism*; D061848:Optical Imaging; D011804:Quinolines / Q000008:administration & dosage; D000068936:Theranostic Nanomedicine / Q000379:methods; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D052160:Benzothiazoles; D003911:Dextrans; D009696:Nucleic Acids; D011804:Quinolines; C051000:thiazole orange
keywords: DNA; Imaging.; Inflammation; Ischemia; Nanoprobe; RNA