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A multi-functional macrophage and tumor targeting gene delivery system for the regulation of macrophage polarity and reversal of cancer immunoresistance
To achieve effective tumor eradication using anti-tumor immunotherapies, a fusion peptide functionalized gene delivery system for macrophage and tumor targeting delivery of the plasmid DNA encoding the IL-12 gene (pDNA IL-12) was prepared for macrophage re-polarization as well as reversal of cancer...
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| Published in: | Nanoscale 2018-01, Vol.10 (33), p.15578-15587 |
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| cites | cdi_FETCH-LOGICAL-c393t-16e5adc053b205c3fcc3a7353fbf9bd94b1727404516ec179941899e123543e53 |
| container_end_page | 15587 |
| container_issue | 33 |
| container_start_page | 15578 |
| container_title | Nanoscale |
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| creator | He, Xiao-Yan Liu, Bo-Ya Xu, Chang Zhuo, Ren-Xi Cheng, Si-Xue |
| description | To achieve effective tumor eradication using anti-tumor immunotherapies, a fusion peptide functionalized gene delivery system for macrophage and tumor targeting delivery of the plasmid DNA encoding the IL-12 gene (pDNA IL-12) was prepared for macrophage re-polarization as well as reversal of cancer immunosuppression. A fusion peptide containing the tuftsin sequence that can interact with Fc receptors and neuropilin-1, and hyaluronic acid (HA) that can interact with CD44 were introduced into the delivery system by self-assembly to form peptide/hyaluronic acid/protamine/CaCO3/DNA nanoparticles (PHNP) with both macrophage targeting and tumor targeting capabilities. PHNP provides an efficient immunoregulation on J774A.1 cells to shift the anti-inflammatory M2 phenotype to the anti-tumor M1 phenotype with enhanced secretion of pro-inflammatory cytokines and increased expression of M1 markers. Owing to the improved delivery efficiency caused by the fusion peptide and HA, the transfection mediated by multi-functional PHNP can up-regulate IL-12 as well as down-regulate IL-10 and IL-4 more effectively as compared with the nanoparticles without HA and/or peptide decoration. More importantly, the gene delivery system can also deliver pDNA IL-12 to targeted cancerous HeLa cells to realize the secretion of IL-12. PHNP not only enables tumorous cells to produce pDNA IL-12, but also down-regulates CD47 and up-regulate CD80 and HLA-1 in the malignant cells, indicating that the gene delivery system can effectively reverse tumor induced immunosuppression. |
| doi_str_mv | 10.1039/c8nr05294h |
| format | article |
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A fusion peptide containing the tuftsin sequence that can interact with Fc receptors and neuropilin-1, and hyaluronic acid (HA) that can interact with CD44 were introduced into the delivery system by self-assembly to form peptide/hyaluronic acid/protamine/CaCO3/DNA nanoparticles (PHNP) with both macrophage targeting and tumor targeting capabilities. PHNP provides an efficient immunoregulation on J774A.1 cells to shift the anti-inflammatory M2 phenotype to the anti-tumor M1 phenotype with enhanced secretion of pro-inflammatory cytokines and increased expression of M1 markers. Owing to the improved delivery efficiency caused by the fusion peptide and HA, the transfection mediated by multi-functional PHNP can up-regulate IL-12 as well as down-regulate IL-10 and IL-4 more effectively as compared with the nanoparticles without HA and/or peptide decoration. More importantly, the gene delivery system can also deliver pDNA IL-12 to targeted cancerous HeLa cells to realize the secretion of IL-12. PHNP not only enables tumorous cells to produce pDNA IL-12, but also down-regulates CD47 and up-regulate CD80 and HLA-1 in the malignant cells, indicating that the gene delivery system can effectively reverse tumor induced immunosuppression.</description><identifier>ISSN: 2040-3364</identifier><identifier>EISSN: 2040-3372</identifier><identifier>DOI: 10.1039/c8nr05294h</identifier><identifier>PMID: 30090893</identifier><language>eng</language><publisher>England: Royal Society of Chemistry</publisher><subject>Animals ; Anticancer properties ; Calcium carbonate ; Cancer ; Cell Line ; Cell Polarity ; Cytokines ; Deoxyribonucleic acid ; DNA ; Gene expression ; Gene Transfer Techniques ; HEK293 Cells ; HeLa Cells ; Humans ; Hyaluronan Receptors ; Hyaluronic Acid ; Immunosuppression ; Interleukin-12 - genetics ; Macrophages - cytology ; Mice ; Nanoparticles ; Neuropilin-1 ; Peptides ; Plasmids ; Polarity ; Protamines ; Receptors ; Receptors, Fc ; Recombinant Fusion Proteins ; Self-assembly ; Transfection ; Tuftsin ; Tumor Microenvironment ; Tumors</subject><ispartof>Nanoscale, 2018-01, Vol.10 (33), p.15578-15587</ispartof><rights>Copyright Royal Society of Chemistry 2018</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c393t-16e5adc053b205c3fcc3a7353fbf9bd94b1727404516ec179941899e123543e53</citedby><cites>FETCH-LOGICAL-c393t-16e5adc053b205c3fcc3a7353fbf9bd94b1727404516ec179941899e123543e53</cites><orcidid>0000-0001-9611-4421</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30090893$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>He, Xiao-Yan</creatorcontrib><creatorcontrib>Liu, Bo-Ya</creatorcontrib><creatorcontrib>Xu, Chang</creatorcontrib><creatorcontrib>Zhuo, Ren-Xi</creatorcontrib><creatorcontrib>Cheng, Si-Xue</creatorcontrib><title>A multi-functional macrophage and tumor targeting gene delivery system for the regulation of macrophage polarity and reversal of cancer immunoresistance</title><title>Nanoscale</title><addtitle>Nanoscale</addtitle><description>To achieve effective tumor eradication using anti-tumor immunotherapies, a fusion peptide functionalized gene delivery system for macrophage and tumor targeting delivery of the plasmid DNA encoding the IL-12 gene (pDNA IL-12) was prepared for macrophage re-polarization as well as reversal of cancer immunosuppression. A fusion peptide containing the tuftsin sequence that can interact with Fc receptors and neuropilin-1, and hyaluronic acid (HA) that can interact with CD44 were introduced into the delivery system by self-assembly to form peptide/hyaluronic acid/protamine/CaCO3/DNA nanoparticles (PHNP) with both macrophage targeting and tumor targeting capabilities. PHNP provides an efficient immunoregulation on J774A.1 cells to shift the anti-inflammatory M2 phenotype to the anti-tumor M1 phenotype with enhanced secretion of pro-inflammatory cytokines and increased expression of M1 markers. Owing to the improved delivery efficiency caused by the fusion peptide and HA, the transfection mediated by multi-functional PHNP can up-regulate IL-12 as well as down-regulate IL-10 and IL-4 more effectively as compared with the nanoparticles without HA and/or peptide decoration. 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PHNP not only enables tumorous cells to produce pDNA IL-12, but also down-regulates CD47 and up-regulate CD80 and HLA-1 in the malignant cells, indicating that the gene delivery system can effectively reverse tumor induced immunosuppression.</description><subject>Animals</subject><subject>Anticancer properties</subject><subject>Calcium carbonate</subject><subject>Cancer</subject><subject>Cell Line</subject><subject>Cell Polarity</subject><subject>Cytokines</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>Gene expression</subject><subject>Gene Transfer Techniques</subject><subject>HEK293 Cells</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Hyaluronan Receptors</subject><subject>Hyaluronic Acid</subject><subject>Immunosuppression</subject><subject>Interleukin-12 - genetics</subject><subject>Macrophages - cytology</subject><subject>Mice</subject><subject>Nanoparticles</subject><subject>Neuropilin-1</subject><subject>Peptides</subject><subject>Plasmids</subject><subject>Polarity</subject><subject>Protamines</subject><subject>Receptors</subject><subject>Receptors, Fc</subject><subject>Recombinant Fusion Proteins</subject><subject>Self-assembly</subject><subject>Transfection</subject><subject>Tuftsin</subject><subject>Tumor Microenvironment</subject><subject>Tumors</subject><issn>2040-3364</issn><issn>2040-3372</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNpd0V9r1TAYBvAiDjenN34ACXgzhGqSt02by3FwThgORK9Lmr7tyWiSY_4I55v4cU23OURykRB-eULyVNUbRj8wCvKj7l2gLZfN_ll1xmlDa4COP39ai-a0ehnjHaVCgoAX1SlQKmkv4az6fUlsXpOp5-x0Mt6plVilgz_s1YJEuYmkbH0gSYUFk3ELWdAhmXA1vzAcSTzGhJbMG9kjCbjkVW1BxM__Jh38qoJJx_vIgOVsLFcVo5XTGIixNjsfMJqYtp1X1cms1oivH-fz6sfVp--76_rm9vOX3eVNrUFCqpnAVk2atjBy2mqYtQbVQQvzOMtxks3IOt41tGmL1KyTsmG9lMg4tA1gC-fVxUPuIfifGWMarIka11U59DkOnPaClyFYoe_-o3c-h_Jjm5KcCSl6UdT7B1WeHmPAeTgEY1U4DowOW1_Drv_67b6v64LfPkbm0eL0RP8WBH8AycGSyg</recordid><startdate>20180101</startdate><enddate>20180101</enddate><creator>He, Xiao-Yan</creator><creator>Liu, Bo-Ya</creator><creator>Xu, Chang</creator><creator>Zhuo, Ren-Xi</creator><creator>Cheng, Si-Xue</creator><general>Royal Society of Chemistry</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>7SR</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>F28</scope><scope>FR3</scope><scope>JG9</scope><scope>L7M</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-9611-4421</orcidid></search><sort><creationdate>20180101</creationdate><title>A multi-functional macrophage and tumor targeting gene delivery system for the regulation of macrophage polarity and reversal of cancer immunoresistance</title><author>He, Xiao-Yan ; Liu, Bo-Ya ; Xu, Chang ; Zhuo, Ren-Xi ; Cheng, Si-Xue</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c393t-16e5adc053b205c3fcc3a7353fbf9bd94b1727404516ec179941899e123543e53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Animals</topic><topic>Anticancer properties</topic><topic>Calcium carbonate</topic><topic>Cancer</topic><topic>Cell Line</topic><topic>Cell Polarity</topic><topic>Cytokines</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>Gene expression</topic><topic>Gene Transfer Techniques</topic><topic>HEK293 Cells</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>Hyaluronan Receptors</topic><topic>Hyaluronic Acid</topic><topic>Immunosuppression</topic><topic>Interleukin-12 - genetics</topic><topic>Macrophages - cytology</topic><topic>Mice</topic><topic>Nanoparticles</topic><topic>Neuropilin-1</topic><topic>Peptides</topic><topic>Plasmids</topic><topic>Polarity</topic><topic>Protamines</topic><topic>Receptors</topic><topic>Receptors, Fc</topic><topic>Recombinant Fusion Proteins</topic><topic>Self-assembly</topic><topic>Transfection</topic><topic>Tuftsin</topic><topic>Tumor Microenvironment</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>He, Xiao-Yan</creatorcontrib><creatorcontrib>Liu, Bo-Ya</creatorcontrib><creatorcontrib>Xu, Chang</creatorcontrib><creatorcontrib>Zhuo, Ren-Xi</creatorcontrib><creatorcontrib>Cheng, Si-Xue</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Engineered Materials Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Engineering Research Database</collection><collection>Materials Research Database</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>MEDLINE - Academic</collection><jtitle>Nanoscale</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>He, Xiao-Yan</au><au>Liu, Bo-Ya</au><au>Xu, Chang</au><au>Zhuo, Ren-Xi</au><au>Cheng, Si-Xue</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A multi-functional macrophage and tumor targeting gene delivery system for the regulation of macrophage polarity and reversal of cancer immunoresistance</atitle><jtitle>Nanoscale</jtitle><addtitle>Nanoscale</addtitle><date>2018-01-01</date><risdate>2018</risdate><volume>10</volume><issue>33</issue><spage>15578</spage><epage>15587</epage><pages>15578-15587</pages><issn>2040-3364</issn><eissn>2040-3372</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>To achieve effective tumor eradication using anti-tumor immunotherapies, a fusion peptide functionalized gene delivery system for macrophage and tumor targeting delivery of the plasmid DNA encoding the IL-12 gene (pDNA IL-12) was prepared for macrophage re-polarization as well as reversal of cancer immunosuppression. A fusion peptide containing the tuftsin sequence that can interact with Fc receptors and neuropilin-1, and hyaluronic acid (HA) that can interact with CD44 were introduced into the delivery system by self-assembly to form peptide/hyaluronic acid/protamine/CaCO3/DNA nanoparticles (PHNP) with both macrophage targeting and tumor targeting capabilities. PHNP provides an efficient immunoregulation on J774A.1 cells to shift the anti-inflammatory M2 phenotype to the anti-tumor M1 phenotype with enhanced secretion of pro-inflammatory cytokines and increased expression of M1 markers. Owing to the improved delivery efficiency caused by the fusion peptide and HA, the transfection mediated by multi-functional PHNP can up-regulate IL-12 as well as down-regulate IL-10 and IL-4 more effectively as compared with the nanoparticles without HA and/or peptide decoration. More importantly, the gene delivery system can also deliver pDNA IL-12 to targeted cancerous HeLa cells to realize the secretion of IL-12. PHNP not only enables tumorous cells to produce pDNA IL-12, but also down-regulates CD47 and up-regulate CD80 and HLA-1 in the malignant cells, indicating that the gene delivery system can effectively reverse tumor induced immunosuppression.</abstract><cop>England</cop><pub>Royal Society of Chemistry</pub><pmid>30090893</pmid><doi>10.1039/c8nr05294h</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0001-9611-4421</orcidid></addata></record> |
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| ispartof | Nanoscale, 2018-01, Vol.10 (33), p.15578-15587 |
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| language | eng |
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| source | Royal Society of Chemistry:Jisc Collections:Royal Society of Chemistry Read and Publish 2022-2024 (reading list) |
| subjects | Animals Anticancer properties Calcium carbonate Cancer Cell Line Cell Polarity Cytokines Deoxyribonucleic acid DNA Gene expression Gene Transfer Techniques HEK293 Cells HeLa Cells Humans Hyaluronan Receptors Hyaluronic Acid Immunosuppression Interleukin-12 - genetics Macrophages - cytology Mice Nanoparticles Neuropilin-1 Peptides Plasmids Polarity Protamines Receptors Receptors, Fc Recombinant Fusion Proteins Self-assembly Transfection Tuftsin Tumor Microenvironment Tumors |
| title | A multi-functional macrophage and tumor targeting gene delivery system for the regulation of macrophage polarity and reversal of cancer immunoresistance |
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