Protection against TNFα-dependent liver toxicity by intraperitoneal liposome delivered DsiRNA targeting TNFα in vivo
Tumor necrosis factor-alpha (TNFα) is a classic proinflammatory cytokine implicated in the pathogenesis of several autoimmune and inflammatory diseases including viral encephalitis. Macrophages being major producers of TNFα are thus attractive targets for in vivo RNA interference (RNAi) mediated dow...
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| Veröffentlicht in: | Journal of controlled release 2012-06, Vol.160 (2), p.194-199 |
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| creator | Lundberg, Patric Yang, Hui-Jung Jung, Seung-Jae Behlke, Mark A. Rose, Scott D. Cantin, Edouard M. |
| description | Tumor necrosis factor-alpha (TNFα) is a classic proinflammatory cytokine implicated in the pathogenesis of several autoimmune and inflammatory diseases including viral encephalitis. Macrophages being major producers of TNFα are thus attractive targets for in vivo RNA interference (RNAi) mediated down regulation of TNFα. The application of RNAi technology to in vivo models however presents obstacles, including rapid degradation of RNA duplexes in plasma, insufficient delivery to the target cell population and toxicity associated with intravenous administration of synthetic RNAs and carrier compounds.
We exploited the phagocytic ability of macrophages for delivery of Dicer-substrate small interfering RNAs (DsiRNAs) targeting TNFα (DsiTNFα) by intraperitoneal administration of lipid–DsiRNA complexes that were efficiently taken up by peritoneal macrophages and other phagocytic cells. We report that DsiTNFα–lipid complexes delivered intraperitoneally altered the disease outcome in an acute sepsis model. Down-regulation of TNFα in peritoneal CD11b+ monocytes reduced liver damage in C57BL/6 mice and significantly delayed acute mortality in mice treated with low dose LPS plus d-galactosamine (D-GalN).
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| doi_str_mv | 10.1016/j.jconrel.2011.10.034 |
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We exploited the phagocytic ability of macrophages for delivery of Dicer-substrate small interfering RNAs (DsiRNAs) targeting TNFα (DsiTNFα) by intraperitoneal administration of lipid–DsiRNA complexes that were efficiently taken up by peritoneal macrophages and other phagocytic cells. We report that DsiTNFα–lipid complexes delivered intraperitoneally altered the disease outcome in an acute sepsis model. Down-regulation of TNFα in peritoneal CD11b+ monocytes reduced liver damage in C57BL/6 mice and significantly delayed acute mortality in mice treated with low dose LPS plus d-galactosamine (D-GalN).
[Display omitted]</description><identifier>ISSN: 0168-3659</identifier><identifier>EISSN: 1873-4995</identifier><identifier>DOI: 10.1016/j.jconrel.2011.10.034</identifier><identifier>PMID: 22094102</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Animal studies ; Animals ; CD11b Antigen - metabolism ; Cell Culture Techniques ; Cell Line ; Chemical and Drug Induced Liver Injury - epidemiology ; Chemical and Drug Induced Liver Injury - genetics ; Chemical and Drug Induced Liver Injury - immunology ; Chemical and Drug Induced Liver Injury - prevention & control ; DEAD-box RNA Helicases - metabolism ; Disease Models, Animal ; Down-Regulation ; Flow Cytometry ; Galactosamine - pharmacology ; hepatotoxicity ; In vivo siRNA ; Injections, Intraperitoneal ; intraperitoneal injection ; intravenous injection ; Lipopolysaccharides - pharmacology ; Liposomes ; liver ; macrophages ; Macrophages - drug effects ; Macrophages - immunology ; Macrophages - metabolism ; Mice ; Mice, Inbred C57BL ; monocytes ; Monocytes - drug effects ; Monocytes - immunology ; mortality ; pathogenesis ; phagocytosis ; Ribonuclease III - metabolism ; RNA ; RNA interference ; RNA, Small Interfering - administration & dosage ; RNA, Small Interfering - genetics ; Sepsis ; sepsis (infection) ; Sepsis - chemically induced ; Sepsis - complications ; Sepsis - immunology ; TNF ; Transfection ; tumor necrosis factor-alpha ; Tumor Necrosis Factor-alpha - antagonists & inhibitors ; Tumor Necrosis Factor-alpha - genetics ; viral encephalitis</subject><ispartof>Journal of controlled release, 2012-06, Vol.160 (2), p.194-199</ispartof><rights>2011 Elsevier B.V.</rights><rights>Copyright © 2011 Elsevier B.V. All rights reserved.</rights><rights>2011 Elsevier B.V. All rights reserved. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c491t-a3c03d8c900ffc944ff343e886913d3cd1e154e6e3c371e1765d1834f77a366d3</citedby><cites>FETCH-LOGICAL-c491t-a3c03d8c900ffc944ff343e886913d3cd1e154e6e3c371e1765d1834f77a366d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jconrel.2011.10.034$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22094102$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lundberg, Patric</creatorcontrib><creatorcontrib>Yang, Hui-Jung</creatorcontrib><creatorcontrib>Jung, Seung-Jae</creatorcontrib><creatorcontrib>Behlke, Mark A.</creatorcontrib><creatorcontrib>Rose, Scott D.</creatorcontrib><creatorcontrib>Cantin, Edouard M.</creatorcontrib><title>Protection against TNFα-dependent liver toxicity by intraperitoneal liposome delivered DsiRNA targeting TNFα in vivo</title><title>Journal of controlled release</title><addtitle>J Control Release</addtitle><description>Tumor necrosis factor-alpha (TNFα) is a classic proinflammatory cytokine implicated in the pathogenesis of several autoimmune and inflammatory diseases including viral encephalitis. Macrophages being major producers of TNFα are thus attractive targets for in vivo RNA interference (RNAi) mediated down regulation of TNFα. The application of RNAi technology to in vivo models however presents obstacles, including rapid degradation of RNA duplexes in plasma, insufficient delivery to the target cell population and toxicity associated with intravenous administration of synthetic RNAs and carrier compounds.
We exploited the phagocytic ability of macrophages for delivery of Dicer-substrate small interfering RNAs (DsiRNAs) targeting TNFα (DsiTNFα) by intraperitoneal administration of lipid–DsiRNA complexes that were efficiently taken up by peritoneal macrophages and other phagocytic cells. We report that DsiTNFα–lipid complexes delivered intraperitoneally altered the disease outcome in an acute sepsis model. Down-regulation of TNFα in peritoneal CD11b+ monocytes reduced liver damage in C57BL/6 mice and significantly delayed acute mortality in mice treated with low dose LPS plus d-galactosamine (D-GalN).
[Display omitted]</description><subject>Animal studies</subject><subject>Animals</subject><subject>CD11b Antigen - metabolism</subject><subject>Cell Culture Techniques</subject><subject>Cell Line</subject><subject>Chemical and Drug Induced Liver Injury - epidemiology</subject><subject>Chemical and Drug Induced Liver Injury - genetics</subject><subject>Chemical and Drug Induced Liver Injury - immunology</subject><subject>Chemical and Drug Induced Liver Injury - prevention & control</subject><subject>DEAD-box RNA Helicases - metabolism</subject><subject>Disease Models, Animal</subject><subject>Down-Regulation</subject><subject>Flow Cytometry</subject><subject>Galactosamine - pharmacology</subject><subject>hepatotoxicity</subject><subject>In vivo siRNA</subject><subject>Injections, Intraperitoneal</subject><subject>intraperitoneal injection</subject><subject>intravenous injection</subject><subject>Lipopolysaccharides - pharmacology</subject><subject>Liposomes</subject><subject>liver</subject><subject>macrophages</subject><subject>Macrophages - drug effects</subject><subject>Macrophages - immunology</subject><subject>Macrophages - metabolism</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>monocytes</subject><subject>Monocytes - drug effects</subject><subject>Monocytes - immunology</subject><subject>mortality</subject><subject>pathogenesis</subject><subject>phagocytosis</subject><subject>Ribonuclease III - metabolism</subject><subject>RNA</subject><subject>RNA interference</subject><subject>RNA, Small Interfering - administration & dosage</subject><subject>RNA, Small Interfering - genetics</subject><subject>Sepsis</subject><subject>sepsis (infection)</subject><subject>Sepsis - chemically induced</subject><subject>Sepsis - complications</subject><subject>Sepsis - immunology</subject><subject>TNF</subject><subject>Transfection</subject><subject>tumor necrosis factor-alpha</subject><subject>Tumor Necrosis Factor-alpha - antagonists & inhibitors</subject><subject>Tumor Necrosis Factor-alpha - genetics</subject><subject>viral encephalitis</subject><issn>0168-3659</issn><issn>1873-4995</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkdFuFCEUhonR2G31EVReYFYYGGa40TTVapOmNdpeEwpnRjazMAE6cR_LF-kzyTpto1e9ghy-_z-H8yP0hpI1JVS836w3JvgI47omlJbamjD-DK1o17KKS9k8R6vCdRUTjTxAhyltCCEN4-1LdFDXRHJK6hWav8WQwWQXPNaDdj5lfHVxeve7sjCBt-AzHt0MEefwyxmXd_hmh53PUU8QXQ4e9FiIKaSwBWzhLwwWf0ru-8UxzjoOkJ0fFteixLObwyv0otdjgtf35xG6Pv18dfK1Or_8cnZyfF4ZLmmuNDOE2c5IQvreSM77nnEGXSckZZYZS4E2HAQww9pyb0Vjacd437aaCWHZEfqw-E63N1uwBvaDj2qKbqvjTgXt1P8v3v1UQ5gVYzVlkhSDZjEwMaQUoX_UUqL2QaiNug9C7YPYl0sQRff238aPqofNF-DdAvQ6KD1El9T1j-LQEFK-IURTiI8LAWVBs4OoknHgDVgXS2LKBvfEEH8AuCiqfQ</recordid><startdate>20120610</startdate><enddate>20120610</enddate><creator>Lundberg, Patric</creator><creator>Yang, Hui-Jung</creator><creator>Jung, Seung-Jae</creator><creator>Behlke, Mark A.</creator><creator>Rose, Scott D.</creator><creator>Cantin, Edouard M.</creator><general>Elsevier B.V</general><scope>FBQ</scope><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>5PM</scope></search><sort><creationdate>20120610</creationdate><title>Protection against TNFα-dependent liver toxicity by intraperitoneal liposome delivered DsiRNA targeting TNFα in vivo</title><author>Lundberg, Patric ; Yang, Hui-Jung ; Jung, Seung-Jae ; Behlke, Mark A. ; Rose, Scott D. ; Cantin, Edouard M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c491t-a3c03d8c900ffc944ff343e886913d3cd1e154e6e3c371e1765d1834f77a366d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Animal studies</topic><topic>Animals</topic><topic>CD11b Antigen - metabolism</topic><topic>Cell Culture Techniques</topic><topic>Cell Line</topic><topic>Chemical and Drug Induced Liver Injury - epidemiology</topic><topic>Chemical and Drug Induced Liver Injury - genetics</topic><topic>Chemical and Drug Induced Liver Injury - immunology</topic><topic>Chemical and Drug Induced Liver Injury - prevention & control</topic><topic>DEAD-box RNA Helicases - metabolism</topic><topic>Disease Models, Animal</topic><topic>Down-Regulation</topic><topic>Flow Cytometry</topic><topic>Galactosamine - pharmacology</topic><topic>hepatotoxicity</topic><topic>In vivo siRNA</topic><topic>Injections, Intraperitoneal</topic><topic>intraperitoneal injection</topic><topic>intravenous injection</topic><topic>Lipopolysaccharides - pharmacology</topic><topic>Liposomes</topic><topic>liver</topic><topic>macrophages</topic><topic>Macrophages - drug effects</topic><topic>Macrophages - immunology</topic><topic>Macrophages - metabolism</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>monocytes</topic><topic>Monocytes - drug effects</topic><topic>Monocytes - immunology</topic><topic>mortality</topic><topic>pathogenesis</topic><topic>phagocytosis</topic><topic>Ribonuclease III - metabolism</topic><topic>RNA</topic><topic>RNA interference</topic><topic>RNA, Small Interfering - administration & dosage</topic><topic>RNA, Small Interfering - genetics</topic><topic>Sepsis</topic><topic>sepsis (infection)</topic><topic>Sepsis - chemically induced</topic><topic>Sepsis - complications</topic><topic>Sepsis - immunology</topic><topic>TNF</topic><topic>Transfection</topic><topic>tumor necrosis factor-alpha</topic><topic>Tumor Necrosis Factor-alpha - antagonists & inhibitors</topic><topic>Tumor Necrosis Factor-alpha - genetics</topic><topic>viral encephalitis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lundberg, Patric</creatorcontrib><creatorcontrib>Yang, Hui-Jung</creatorcontrib><creatorcontrib>Jung, Seung-Jae</creatorcontrib><creatorcontrib>Behlke, Mark A.</creatorcontrib><creatorcontrib>Rose, Scott D.</creatorcontrib><creatorcontrib>Cantin, Edouard M.</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of controlled release</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lundberg, Patric</au><au>Yang, Hui-Jung</au><au>Jung, Seung-Jae</au><au>Behlke, Mark A.</au><au>Rose, Scott D.</au><au>Cantin, Edouard M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Protection against TNFα-dependent liver toxicity by intraperitoneal liposome delivered DsiRNA targeting TNFα in vivo</atitle><jtitle>Journal of controlled release</jtitle><addtitle>J Control Release</addtitle><date>2012-06-10</date><risdate>2012</risdate><volume>160</volume><issue>2</issue><spage>194</spage><epage>199</epage><pages>194-199</pages><issn>0168-3659</issn><eissn>1873-4995</eissn><abstract>Tumor necrosis factor-alpha (TNFα) is a classic proinflammatory cytokine implicated in the pathogenesis of several autoimmune and inflammatory diseases including viral encephalitis. Macrophages being major producers of TNFα are thus attractive targets for in vivo RNA interference (RNAi) mediated down regulation of TNFα. The application of RNAi technology to in vivo models however presents obstacles, including rapid degradation of RNA duplexes in plasma, insufficient delivery to the target cell population and toxicity associated with intravenous administration of synthetic RNAs and carrier compounds.
We exploited the phagocytic ability of macrophages for delivery of Dicer-substrate small interfering RNAs (DsiRNAs) targeting TNFα (DsiTNFα) by intraperitoneal administration of lipid–DsiRNA complexes that were efficiently taken up by peritoneal macrophages and other phagocytic cells. We report that DsiTNFα–lipid complexes delivered intraperitoneally altered the disease outcome in an acute sepsis model. Down-regulation of TNFα in peritoneal CD11b+ monocytes reduced liver damage in C57BL/6 mice and significantly delayed acute mortality in mice treated with low dose LPS plus d-galactosamine (D-GalN).
[Display omitted]</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>22094102</pmid><doi>10.1016/j.jconrel.2011.10.034</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animal studies Animals CD11b Antigen - metabolism Cell Culture Techniques Cell Line Chemical and Drug Induced Liver Injury - epidemiology Chemical and Drug Induced Liver Injury - genetics Chemical and Drug Induced Liver Injury - immunology Chemical and Drug Induced Liver Injury - prevention & control DEAD-box RNA Helicases - metabolism Disease Models, Animal Down-Regulation Flow Cytometry Galactosamine - pharmacology hepatotoxicity In vivo siRNA Injections, Intraperitoneal intraperitoneal injection intravenous injection Lipopolysaccharides - pharmacology Liposomes liver macrophages Macrophages - drug effects Macrophages - immunology Macrophages - metabolism Mice Mice, Inbred C57BL monocytes Monocytes - drug effects Monocytes - immunology mortality pathogenesis phagocytosis Ribonuclease III - metabolism RNA RNA interference RNA, Small Interfering - administration & dosage RNA, Small Interfering - genetics Sepsis sepsis (infection) Sepsis - chemically induced Sepsis - complications Sepsis - immunology TNF Transfection tumor necrosis factor-alpha Tumor Necrosis Factor-alpha - antagonists & inhibitors Tumor Necrosis Factor-alpha - genetics viral encephalitis |
| title | Protection against TNFα-dependent liver toxicity by intraperitoneal liposome delivered DsiRNA targeting TNFα in vivo |
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