Theranostic Nucleic Acid Binding Nanoprobe Exerts Anti-inflammatory and Cytoprotective Effects in Ischemic Injury
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. Dext...
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Veröffentlicht in: | Theranostics 2017-01, Vol.7 (4), p.814-825 |
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creator | Chen, Howard H Yuan, Hushan Cho, Hoonsung Feng, Yan Ngoy, Soeun Kumar, Anand T N Liao, Ronglih Chao, Wei Josephson, Lee Sosnovik, David E |
description | 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 |
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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.</description><identifier>ISSN: 1838-7640</identifier><identifier>EISSN: 1838-7640</identifier><identifier>DOI: 10.7150/thno.17366</identifier><identifier>PMID: 28382156</identifier><language>eng</language><publisher>Australia: Ivyspring International Publisher</publisher><subject>Animals ; Anti-Inflammatory Agents - administration & dosage ; Benzothiazoles - administration & dosage ; Cytoprotection ; Dextrans - administration & dosage ; Mice ; Myocardial Reperfusion Injury - diagnostic imaging ; Myocardial Reperfusion Injury - drug therapy ; Myocardial Reperfusion Injury - pathology ; Nanostructures - administration & dosage ; Nucleic Acids - metabolism ; Optical Imaging ; Quinolines - administration & dosage ; Research Paper ; Theranostic Nanomedicine - methods ; Treatment Outcome</subject><ispartof>Theranostics, 2017-01, Vol.7 (4), p.814-825</ispartof><rights>Ivyspring International Publisher 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c378t-1ef3cc1feec1fea6644ce8a0badf1dc43f08a700338a120ea979aaa5a91fdb813</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5381246/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5381246/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,725,778,782,883,27911,27912,53778,53780</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28382156$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Howard H</creatorcontrib><creatorcontrib>Yuan, Hushan</creatorcontrib><creatorcontrib>Cho, Hoonsung</creatorcontrib><creatorcontrib>Feng, Yan</creatorcontrib><creatorcontrib>Ngoy, Soeun</creatorcontrib><creatorcontrib>Kumar, Anand T N</creatorcontrib><creatorcontrib>Liao, Ronglih</creatorcontrib><creatorcontrib>Chao, Wei</creatorcontrib><creatorcontrib>Josephson, Lee</creatorcontrib><creatorcontrib>Sosnovik, David E</creatorcontrib><title>Theranostic Nucleic Acid Binding Nanoprobe Exerts Anti-inflammatory and Cytoprotective Effects in Ischemic Injury</title><title>Theranostics</title><addtitle>Theranostics</addtitle><description>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.</description><subject>Animals</subject><subject>Anti-Inflammatory Agents - administration & dosage</subject><subject>Benzothiazoles - administration & dosage</subject><subject>Cytoprotection</subject><subject>Dextrans - administration & dosage</subject><subject>Mice</subject><subject>Myocardial Reperfusion Injury - diagnostic imaging</subject><subject>Myocardial Reperfusion Injury - drug therapy</subject><subject>Myocardial Reperfusion Injury - pathology</subject><subject>Nanostructures - administration & dosage</subject><subject>Nucleic Acids - metabolism</subject><subject>Optical Imaging</subject><subject>Quinolines - administration & dosage</subject><subject>Research Paper</subject><subject>Theranostic Nanomedicine - methods</subject><subject>Treatment Outcome</subject><issn>1838-7640</issn><issn>1838-7640</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkUFrGzEQhUVoaILjS39A0bEUNpFW613tpeAaNzEY95KexVg7ihV2JUfShvrfV26ckMxhZuB9vBl4hHzh7LrhM3aTds5f80bU9Rm55FLIoqkr9undfkGmMT6yXBUrW95-Jhdl1ko-qy_J0_0OAzgfk9V0M-oe85xr29Gf1nXWPdBNVvfBb5Eu_2JIkc5dsoV1podhgOTDgYLr6OKQjlhCnexzZo3JW6TW0VXUOxyy7co9juFwRc4N9BGnpzkhf34t7xd3xfr37WoxXxdaNDIVHI3QmhvEY4O6riqNEtgWOsM7XQnDJDSMCSGBlwyhbVoAmEHLTbeVXEzIjxff_bgdsNPoUoBe7YMdIByUB6s-Ks7u1IN_VjMheVnV2eDbySD4pxFjUoONGvseHPoxKi5lJVsuqyaj319QHXyMAc3bGc7UMSZ1jEn9jynDX98_9oa-hiL-ASFAkj0</recordid><startdate>20170101</startdate><enddate>20170101</enddate><creator>Chen, Howard H</creator><creator>Yuan, Hushan</creator><creator>Cho, Hoonsung</creator><creator>Feng, Yan</creator><creator>Ngoy, Soeun</creator><creator>Kumar, Anand T N</creator><creator>Liao, Ronglih</creator><creator>Chao, Wei</creator><creator>Josephson, Lee</creator><creator>Sosnovik, David E</creator><general>Ivyspring International Publisher</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20170101</creationdate><title>Theranostic Nucleic Acid Binding Nanoprobe Exerts Anti-inflammatory and Cytoprotective Effects in Ischemic Injury</title><author>Chen, Howard H ; Yuan, Hushan ; Cho, Hoonsung ; Feng, Yan ; Ngoy, Soeun ; Kumar, Anand T N ; Liao, Ronglih ; Chao, Wei ; Josephson, Lee ; Sosnovik, David E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c378t-1ef3cc1feec1fea6644ce8a0badf1dc43f08a700338a120ea979aaa5a91fdb813</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Animals</topic><topic>Anti-Inflammatory Agents - administration & dosage</topic><topic>Benzothiazoles - administration & dosage</topic><topic>Cytoprotection</topic><topic>Dextrans - administration & dosage</topic><topic>Mice</topic><topic>Myocardial Reperfusion Injury - diagnostic imaging</topic><topic>Myocardial Reperfusion Injury - drug therapy</topic><topic>Myocardial Reperfusion Injury - pathology</topic><topic>Nanostructures - administration & dosage</topic><topic>Nucleic Acids - metabolism</topic><topic>Optical Imaging</topic><topic>Quinolines - administration & dosage</topic><topic>Research Paper</topic><topic>Theranostic Nanomedicine - methods</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Howard H</creatorcontrib><creatorcontrib>Yuan, Hushan</creatorcontrib><creatorcontrib>Cho, Hoonsung</creatorcontrib><creatorcontrib>Feng, Yan</creatorcontrib><creatorcontrib>Ngoy, Soeun</creatorcontrib><creatorcontrib>Kumar, Anand T N</creatorcontrib><creatorcontrib>Liao, Ronglih</creatorcontrib><creatorcontrib>Chao, Wei</creatorcontrib><creatorcontrib>Josephson, Lee</creatorcontrib><creatorcontrib>Sosnovik, David E</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Theranostics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Howard H</au><au>Yuan, Hushan</au><au>Cho, Hoonsung</au><au>Feng, Yan</au><au>Ngoy, Soeun</au><au>Kumar, Anand T N</au><au>Liao, Ronglih</au><au>Chao, Wei</au><au>Josephson, Lee</au><au>Sosnovik, David E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Theranostic Nucleic Acid Binding Nanoprobe Exerts Anti-inflammatory and Cytoprotective Effects in Ischemic Injury</atitle><jtitle>Theranostics</jtitle><addtitle>Theranostics</addtitle><date>2017-01-01</date><risdate>2017</risdate><volume>7</volume><issue>4</issue><spage>814</spage><epage>825</epage><pages>814-825</pages><issn>1838-7640</issn><eissn>1838-7640</eissn><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.</abstract><cop>Australia</cop><pub>Ivyspring International Publisher</pub><pmid>28382156</pmid><doi>10.7150/thno.17366</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Animals Anti-Inflammatory Agents - administration & dosage Benzothiazoles - administration & dosage Cytoprotection Dextrans - administration & dosage Mice Myocardial Reperfusion Injury - diagnostic imaging Myocardial Reperfusion Injury - drug therapy Myocardial Reperfusion Injury - pathology Nanostructures - administration & dosage Nucleic Acids - metabolism Optical Imaging Quinolines - administration & dosage Research Paper Theranostic Nanomedicine - methods Treatment Outcome |
title | Theranostic Nucleic Acid Binding Nanoprobe Exerts Anti-inflammatory and Cytoprotective Effects in Ischemic Injury |
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