Stimulation of human macrophages (THP-1) using Toll-like receptor-2 (TLR-2) agonist decorated nanocarriers
The purpose of this study was to prepare and characterize nanocarrier systems, which allow the application of pDNA vaccines and adjuvants to mucosal vaccination. Chitosan from a vegetal source (Agaricus bisporus) and of GMP quality was used to synthesize the derivative 6-O-carboxymethyl-N,N,N-trimet...
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| Veröffentlicht in: | Journal of drug targeting 2009-09, Vol.17 (8), p.662-670 |
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| creator | Heuking, Simon Adam-Malpel, Sarah Sublet, Emmanuelle Iannitelli, Antonio Stefano, Antonio di Borchard, Gerrit |
| description | The purpose of this study was to prepare and characterize nanocarrier systems, which allow the application of pDNA vaccines and adjuvants to mucosal vaccination. Chitosan from a vegetal source (Agaricus bisporus) and of GMP quality was used to synthesize the derivative 6-O-carboxymethyl-N,N,N-trimethylchitosan (CM-TMC). Toll-like receptor-2 (TLR-2) agonist, Pam3Cys, was synthesized and coupled to CM-TMC through a polyethylene glycol (PEG) spacer. Successively, Pam3Cys decorated nanocarriers were prepared by complexation with plasmid DNA (pDNA) expressing green fluorescence protein (GFP), and characterized with respect to their physicochemical properties and protection of the included plasmid against DNase I enzymatic degradation. In vitro studies using phorbol 12-myristyl 13-acetate (PMA) stimulated macrophage-like THP-1 (mTHP-1) cells were focused on cytotoxicity of both polymers and particles, and their potential to stimulate IL-8 release via the TLR-2 pathway. Our results showed that the TLR-2 functionalized pDNA nanocarriers have the ability to complex and to protect pDNA against enzymatic degradation. pDNA nanocarriers were of around 400 nm in size, and displayed a positive zeta potential of 27.9 ± 1.6 mV. Chitosan, CM-TMC, and Pam3Cys-functionalized CM-TMC polymers displayed cytotoxicity on mTHP1 cells in a concentration-dependent manner, which decreased by 50-fold on complexation with pDNA. In addition, decorated pDNA nanocarriers induced IL-8 secretion by mTHP-1 macrophages, which was increased by 10-fold as compared to nondecorated carriers. |
| doi_str_mv | 10.1080/10611860903106034 |
| format | Article |
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Chitosan from a vegetal source (Agaricus bisporus) and of GMP quality was used to synthesize the derivative 6-O-carboxymethyl-N,N,N-trimethylchitosan (CM-TMC). Toll-like receptor-2 (TLR-2) agonist, Pam3Cys, was synthesized and coupled to CM-TMC through a polyethylene glycol (PEG) spacer. Successively, Pam3Cys decorated nanocarriers were prepared by complexation with plasmid DNA (pDNA) expressing green fluorescence protein (GFP), and characterized with respect to their physicochemical properties and protection of the included plasmid against DNase I enzymatic degradation. In vitro studies using phorbol 12-myristyl 13-acetate (PMA) stimulated macrophage-like THP-1 (mTHP-1) cells were focused on cytotoxicity of both polymers and particles, and their potential to stimulate IL-8 release via the TLR-2 pathway. Our results showed that the TLR-2 functionalized pDNA nanocarriers have the ability to complex and to protect pDNA against enzymatic degradation. pDNA nanocarriers were of around 400 nm in size, and displayed a positive zeta potential of 27.9 ± 1.6 mV. Chitosan, CM-TMC, and Pam3Cys-functionalized CM-TMC polymers displayed cytotoxicity on mTHP1 cells in a concentration-dependent manner, which decreased by 50-fold on complexation with pDNA. In addition, decorated pDNA nanocarriers induced IL-8 secretion by mTHP-1 macrophages, which was increased by 10-fold as compared to nondecorated carriers.</description><identifier>ISSN: 1061-186X</identifier><identifier>EISSN: 1029-2330</identifier><identifier>DOI: 10.1080/10611860903106034</identifier><identifier>PMID: 19694614</identifier><language>eng</language><publisher>London: Informa UK Ltd</publisher><subject>Agaricus - chemistry ; antigen-presenting cells (APC) ; Biological and medical sciences ; Cell Line ; Cell Line, Tumor ; Chitosan ; Chitosan - chemistry ; DNA - administration & dosage ; Dose-Response Relationship, Drug ; General pharmacology ; Green Fluorescent Proteins - genetics ; Humans ; IL-8 release ; Interleukin-8 - metabolism ; Lipoproteins - chemistry ; Macrophages - metabolism ; Medical sciences ; mucosal vaccination ; Nanoparticles ; Particle Size ; Pharmaceutical technology. Pharmaceutical industry ; Pharmacology. Drug treatments ; Plasmids - administration & dosage ; Polyethylene Glycols - chemistry ; THP-1 macrophages ; Toll-like receptor (TLR) ; Toll-Like Receptor 2 - agonists</subject><ispartof>Journal of drug targeting, 2009-09, Vol.17 (8), p.662-670</ispartof><rights>2009 Informa UK Ltd 2009</rights><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c434t-580e11efe4a0eaa62f3e72252c353500c24d72ec43a698b71de0e4de50a761a3</citedby><cites>FETCH-LOGICAL-c434t-580e11efe4a0eaa62f3e72252c353500c24d72ec43a698b71de0e4de50a761a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.tandfonline.com/doi/pdf/10.1080/10611860903106034$$EPDF$$P50$$Ginformaworld$$H</linktopdf><linktohtml>$$Uhttps://www.tandfonline.com/doi/full/10.1080/10611860903106034$$EHTML$$P50$$Ginformaworld$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,59647,59753,60436,60542,61221,61256,61402,61437</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21946704$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19694614$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Heuking, Simon</creatorcontrib><creatorcontrib>Adam-Malpel, Sarah</creatorcontrib><creatorcontrib>Sublet, Emmanuelle</creatorcontrib><creatorcontrib>Iannitelli, Antonio</creatorcontrib><creatorcontrib>Stefano, Antonio di</creatorcontrib><creatorcontrib>Borchard, Gerrit</creatorcontrib><title>Stimulation of human macrophages (THP-1) using Toll-like receptor-2 (TLR-2) agonist decorated nanocarriers</title><title>Journal of drug targeting</title><addtitle>J Drug Target</addtitle><description>The purpose of this study was to prepare and characterize nanocarrier systems, which allow the application of pDNA vaccines and adjuvants to mucosal vaccination. Chitosan from a vegetal source (Agaricus bisporus) and of GMP quality was used to synthesize the derivative 6-O-carboxymethyl-N,N,N-trimethylchitosan (CM-TMC). Toll-like receptor-2 (TLR-2) agonist, Pam3Cys, was synthesized and coupled to CM-TMC through a polyethylene glycol (PEG) spacer. Successively, Pam3Cys decorated nanocarriers were prepared by complexation with plasmid DNA (pDNA) expressing green fluorescence protein (GFP), and characterized with respect to their physicochemical properties and protection of the included plasmid against DNase I enzymatic degradation. In vitro studies using phorbol 12-myristyl 13-acetate (PMA) stimulated macrophage-like THP-1 (mTHP-1) cells were focused on cytotoxicity of both polymers and particles, and their potential to stimulate IL-8 release via the TLR-2 pathway. Our results showed that the TLR-2 functionalized pDNA nanocarriers have the ability to complex and to protect pDNA against enzymatic degradation. pDNA nanocarriers were of around 400 nm in size, and displayed a positive zeta potential of 27.9 ± 1.6 mV. Chitosan, CM-TMC, and Pam3Cys-functionalized CM-TMC polymers displayed cytotoxicity on mTHP1 cells in a concentration-dependent manner, which decreased by 50-fold on complexation with pDNA. In addition, decorated pDNA nanocarriers induced IL-8 secretion by mTHP-1 macrophages, which was increased by 10-fold as compared to nondecorated carriers.</description><subject>Agaricus - chemistry</subject><subject>antigen-presenting cells (APC)</subject><subject>Biological and medical sciences</subject><subject>Cell Line</subject><subject>Cell Line, Tumor</subject><subject>Chitosan</subject><subject>Chitosan - chemistry</subject><subject>DNA - administration & dosage</subject><subject>Dose-Response Relationship, Drug</subject><subject>General pharmacology</subject><subject>Green Fluorescent Proteins - genetics</subject><subject>Humans</subject><subject>IL-8 release</subject><subject>Interleukin-8 - metabolism</subject><subject>Lipoproteins - chemistry</subject><subject>Macrophages - metabolism</subject><subject>Medical sciences</subject><subject>mucosal vaccination</subject><subject>Nanoparticles</subject><subject>Particle Size</subject><subject>Pharmaceutical technology. Pharmaceutical industry</subject><subject>Pharmacology. Drug treatments</subject><subject>Plasmids - administration & dosage</subject><subject>Polyethylene Glycols - chemistry</subject><subject>THP-1 macrophages</subject><subject>Toll-like receptor (TLR)</subject><subject>Toll-Like Receptor 2 - agonists</subject><issn>1061-186X</issn><issn>1029-2330</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp90MFu1DAQBuAIgWgpPAAX5AuIHgIzduIkgguqgCJVAsEeuEVTZ7LrxbG3diLUt8erXUAIqSfP4ftHnr8oniK8QmjhNYJGbDV0oPIIqrpXnCLIrpRKwf39rLHM4PtJ8SilLQAqjfCwOMFOd5XG6rTYfpvttDiabfAijGKzTOTFRCaG3YbWnMTL1eWXEs_Fkqxfi1VwrnT2B4vIhndziKXM5OprKc8FrYO3aRYDmxBp5kF48sFQjJZjelw8GMklfnJ8z4rVh_eri8vy6vPHTxfvrkpTqWou6xYYkUeuCJhIy1FxI2UtjapVDWBkNTSSMybdtdcNDgxcDVwDNRpJnRUvDmt3MdwsnOZ-ssmwc-Q5LKnXTd3ptmszxAPMt6YUeex30U4Ub3uEft9v_1-_OfPsuHy5nnj4mzgWmsHzI6BkyI2RvLHpj5OYWQN79_bgrB9DnOhniG7oZ7p1If4Oqbv-8eaf-IbJzZvcNPfbsESf-73jil8EKKaJ</recordid><startdate>20090901</startdate><enddate>20090901</enddate><creator>Heuking, Simon</creator><creator>Adam-Malpel, Sarah</creator><creator>Sublet, Emmanuelle</creator><creator>Iannitelli, Antonio</creator><creator>Stefano, Antonio di</creator><creator>Borchard, Gerrit</creator><general>Informa UK Ltd</general><general>Taylor & Francis</general><general>Informa Healthcare</general><scope>IQODW</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>7X8</scope></search><sort><creationdate>20090901</creationdate><title>Stimulation of human macrophages (THP-1) using Toll-like receptor-2 (TLR-2) agonist decorated nanocarriers</title><author>Heuking, Simon ; Adam-Malpel, Sarah ; Sublet, Emmanuelle ; Iannitelli, Antonio ; Stefano, Antonio di ; Borchard, Gerrit</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c434t-580e11efe4a0eaa62f3e72252c353500c24d72ec43a698b71de0e4de50a761a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Agaricus - chemistry</topic><topic>antigen-presenting cells (APC)</topic><topic>Biological and medical sciences</topic><topic>Cell Line</topic><topic>Cell Line, Tumor</topic><topic>Chitosan</topic><topic>Chitosan - chemistry</topic><topic>DNA - administration & dosage</topic><topic>Dose-Response Relationship, Drug</topic><topic>General pharmacology</topic><topic>Green Fluorescent Proteins - genetics</topic><topic>Humans</topic><topic>IL-8 release</topic><topic>Interleukin-8 - metabolism</topic><topic>Lipoproteins - chemistry</topic><topic>Macrophages - metabolism</topic><topic>Medical sciences</topic><topic>mucosal vaccination</topic><topic>Nanoparticles</topic><topic>Particle Size</topic><topic>Pharmaceutical technology. Pharmaceutical industry</topic><topic>Pharmacology. Drug treatments</topic><topic>Plasmids - administration & dosage</topic><topic>Polyethylene Glycols - chemistry</topic><topic>THP-1 macrophages</topic><topic>Toll-like receptor (TLR)</topic><topic>Toll-Like Receptor 2 - agonists</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Heuking, Simon</creatorcontrib><creatorcontrib>Adam-Malpel, Sarah</creatorcontrib><creatorcontrib>Sublet, Emmanuelle</creatorcontrib><creatorcontrib>Iannitelli, Antonio</creatorcontrib><creatorcontrib>Stefano, Antonio di</creatorcontrib><creatorcontrib>Borchard, Gerrit</creatorcontrib><collection>Pascal-Francis</collection><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><jtitle>Journal of drug targeting</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Heuking, Simon</au><au>Adam-Malpel, Sarah</au><au>Sublet, Emmanuelle</au><au>Iannitelli, Antonio</au><au>Stefano, Antonio di</au><au>Borchard, Gerrit</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Stimulation of human macrophages (THP-1) using Toll-like receptor-2 (TLR-2) agonist decorated nanocarriers</atitle><jtitle>Journal of drug targeting</jtitle><addtitle>J Drug Target</addtitle><date>2009-09-01</date><risdate>2009</risdate><volume>17</volume><issue>8</issue><spage>662</spage><epage>670</epage><pages>662-670</pages><issn>1061-186X</issn><eissn>1029-2330</eissn><abstract>The purpose of this study was to prepare and characterize nanocarrier systems, which allow the application of pDNA vaccines and adjuvants to mucosal vaccination. Chitosan from a vegetal source (Agaricus bisporus) and of GMP quality was used to synthesize the derivative 6-O-carboxymethyl-N,N,N-trimethylchitosan (CM-TMC). Toll-like receptor-2 (TLR-2) agonist, Pam3Cys, was synthesized and coupled to CM-TMC through a polyethylene glycol (PEG) spacer. Successively, Pam3Cys decorated nanocarriers were prepared by complexation with plasmid DNA (pDNA) expressing green fluorescence protein (GFP), and characterized with respect to their physicochemical properties and protection of the included plasmid against DNase I enzymatic degradation. In vitro studies using phorbol 12-myristyl 13-acetate (PMA) stimulated macrophage-like THP-1 (mTHP-1) cells were focused on cytotoxicity of both polymers and particles, and their potential to stimulate IL-8 release via the TLR-2 pathway. Our results showed that the TLR-2 functionalized pDNA nanocarriers have the ability to complex and to protect pDNA against enzymatic degradation. pDNA nanocarriers were of around 400 nm in size, and displayed a positive zeta potential of 27.9 ± 1.6 mV. Chitosan, CM-TMC, and Pam3Cys-functionalized CM-TMC polymers displayed cytotoxicity on mTHP1 cells in a concentration-dependent manner, which decreased by 50-fold on complexation with pDNA. In addition, decorated pDNA nanocarriers induced IL-8 secretion by mTHP-1 macrophages, which was increased by 10-fold as compared to nondecorated carriers.</abstract><cop>London</cop><pub>Informa UK Ltd</pub><pmid>19694614</pmid><doi>10.1080/10611860903106034</doi><tpages>9</tpages></addata></record> |
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| ispartof | Journal of drug targeting, 2009-09, Vol.17 (8), p.662-670 |
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| source | MEDLINE; Taylor & Francis Medical Library - CRKN; Access via Taylor & Francis |
| subjects | Agaricus - chemistry antigen-presenting cells (APC) Biological and medical sciences Cell Line Cell Line, Tumor Chitosan Chitosan - chemistry DNA - administration & dosage Dose-Response Relationship, Drug General pharmacology Green Fluorescent Proteins - genetics Humans IL-8 release Interleukin-8 - metabolism Lipoproteins - chemistry Macrophages - metabolism Medical sciences mucosal vaccination Nanoparticles Particle Size Pharmaceutical technology. Pharmaceutical industry Pharmacology. Drug treatments Plasmids - administration & dosage Polyethylene Glycols - chemistry THP-1 macrophages Toll-like receptor (TLR) Toll-Like Receptor 2 - agonists |
| title | Stimulation of human macrophages (THP-1) using Toll-like receptor-2 (TLR-2) agonist decorated nanocarriers |
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