PMID- 28382156 OWN - NLM STAT- MEDLINE DCOM- 20171024 LR - 20221123 IS - 1838-7640 (Electronic) IS - 1838-7640 (Linking) VI - 7 IP - 4 DP - 2017 TI - Theranostic Nucleic Acid Binding Nanoprobe Exerts Anti-inflammatory and Cytoprotective Effects in Ischemic Injury. PG - 814-825 LID - 10.7150/thno.17366 [doi] AB - 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. FAU - Chen, Howard H AU - Chen HH AD - Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston MA;; Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston MA. FAU - Yuan, Hushan AU - Yuan H AD - 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). FAU - Cho, Hoonsung AU - Cho H AD - 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). FAU - Feng, Yan AU - Feng Y AD - 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). FAU - Ngoy, Soeun AU - Ngoy S AD - Division of Genetics and Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston MA. FAU - Kumar, Anand T N AU - Kumar AT AD - Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston MA. FAU - Liao, Ronglih AU - Liao R AD - Division of Genetics and Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston MA. FAU - Chao, Wei AU - Chao W AD - 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). FAU - Josephson, Lee AU - Josephson L AD - 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). FAU - Sosnovik, David E AU - Sosnovik DE AD - Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston MA;; Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston MA. LA - eng GR - R01 HL093038/HL/NHLBI NIH HHS/United States GR - R01 HL112831/HL/NHLBI NIH HHS/United States GR - R00 HL121152/HL/NHLBI NIH HHS/United States GR - R01 GM117233/GM/NIGMS NIH HHS/United States GR - K99 HL121152/HL/NHLBI NIH HHS/United States GR - R01 EB011996/EB/NIBIB NIH HHS/United States GR - S10 RR025504/RR/NCRR NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20170208 PL - Australia TA - Theranostics JT - Theranostics JID - 101552395 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Benzothiazoles) RN - 0 (Dextrans) RN - 0 (Nucleic Acids) RN - 0 (Quinolines) RN - 107091-89-4 (thiazole orange) SB - IM MH - Animals MH - Anti-Inflammatory Agents/*administration & dosage MH - Benzothiazoles/administration & dosage MH - *Cytoprotection MH - Dextrans/administration & dosage MH - Mice MH - Myocardial Reperfusion Injury/diagnostic imaging/*drug therapy/pathology MH - Nanostructures/*administration & dosage MH - Nucleic Acids/*metabolism MH - Optical Imaging MH - Quinolines/administration & dosage MH - Theranostic Nanomedicine/methods MH - Treatment Outcome PMC - PMC5381246 OTO - NOTNLM OT - DNA OT - Imaging. OT - Inflammation OT - Ischemia OT - Nanoprobe OT - RNA COIS- Competing Interests: The authors have declared that no competing interest exists. EDAT- 2017/04/07 06:00 MHDA- 2017/10/25 06:00 PMCR- 2017/01/01 CRDT- 2017/04/07 06:00 PHST- 2016/08/27 00:00 [received] PHST- 2016/11/25 00:00 [accepted] PHST- 2017/04/07 06:00 [entrez] PHST- 2017/04/07 06:00 [pubmed] PHST- 2017/10/25 06:00 [medline] PHST- 2017/01/01 00:00 [pmc-release] AID - thnov07p0814 [pii] AID - 10.7150/thno.17366 [doi] PST - epublish SO - Theranostics. 2017 Feb 8;7(4):814-825. doi: 10.7150/thno.17366. eCollection 2017.