Cancer gene therapy by IL-12 gene delivery using liposomal bubbles and tumoral ultrasound exposure
Interleukin-12 (IL-12) gene therapy is expected to be effective against cancers because it primes the immune system for cancer cells. In this therapy, it is important to induce IL-12 gene expression in the tumor tissue. Sonoporation is an attractive technique for developing non-invasive and non-vira...
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| Veröffentlicht in: | Journal of controlled release 2010-03, Vol.142 (2), p.245-250 |
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| creator | Suzuki, Ryo Namai, Eisuke Oda, Yusuke Nishiie, Norihito Otake, Shota Koshima, Risa Hirata, Keiichi Taira, Yuichiro Utoguchi, Naoki Negishi, Yoichi Nakagawa, Shinsaku Maruyama, Kazuo |
| description | Interleukin-12 (IL-12) gene therapy is expected to be effective against cancers because it primes the immune system for cancer cells. In this therapy, it is important to induce IL-12 gene expression in the tumor tissue. Sonoporation is an attractive technique for developing non-invasive and non-viral gene delivery systems, but simple sonoporation using only ultrasound is not an effective cancer gene therapy because of the low efficiency of gene delivery. We addressed this problem by combining ultrasound and novel ultrasound-sensitive liposomes (Bubble liposomes) which contain the ultrasound imaging gas perfluoropropane. Our previous work showed that this is an effective gene delivery system, and that Bubble liposome collapse (cavitation) is induced by ultrasound exposure. In this study, we assessed the utility of this system in cancer gene therapy using IL-12 corded plasmid DNA. The combination of Bubble liposomes and ultrasound dramatically suppressed tumor growth. This therapeutic effect was T-cell dependent, requiring mainly CD8(+) T lymphocytes in the effector phase, as confirmed by a mouse in vivo depletion assay. In addition, migration of CD8(+) T cells was observed in the mice, indicating that the combination of Bubble liposomes and ultrasound is a good non-viral vector system in IL-12 cancer gene therapy. |
| doi_str_mv | 10.1016/j.jconrel.2009.10.027 |
| format | Article |
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In this therapy, it is important to induce IL-12 gene expression in the tumor tissue. Sonoporation is an attractive technique for developing non-invasive and non-viral gene delivery systems, but simple sonoporation using only ultrasound is not an effective cancer gene therapy because of the low efficiency of gene delivery. We addressed this problem by combining ultrasound and novel ultrasound-sensitive liposomes (Bubble liposomes) which contain the ultrasound imaging gas perfluoropropane. Our previous work showed that this is an effective gene delivery system, and that Bubble liposome collapse (cavitation) is induced by ultrasound exposure. In this study, we assessed the utility of this system in cancer gene therapy using IL-12 corded plasmid DNA. The combination of Bubble liposomes and ultrasound dramatically suppressed tumor growth. This therapeutic effect was T-cell dependent, requiring mainly CD8(+) T lymphocytes in the effector phase, as confirmed by a mouse in vivo depletion assay. In addition, migration of CD8(+) T cells was observed in the mice, indicating that the combination of Bubble liposomes and ultrasound is a good non-viral vector system in IL-12 cancer gene therapy.</description><identifier>ISSN: 0168-3659</identifier><identifier>EISSN: 1873-4995</identifier><identifier>DOI: 10.1016/j.jconrel.2009.10.027</identifier><identifier>PMID: 19883708</identifier><language>eng</language><publisher>Netherlands</publisher><subject>Animals ; Cancer ; Carcinoma - therapy ; Cavitation ; CD8 antigen ; Controlled release ; DNA ; DNA - administration & dosage ; Expression vectors ; Female ; Gene Expression ; Gene therapy ; Gene transfer ; Gene Transfer Techniques ; Genetic Therapy - methods ; imaging ; Immune system ; Interleukin 12 ; Interleukin-12 - genetics ; Leukocyte migration ; Liposomes ; Liposomes - chemistry ; Lymphocytes T ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Ovarian Neoplasms - therapy ; Plasmids ; Plasmids - administration & dosage ; Transfection ; Tumors ; Ultrasonics ; Ultrasound</subject><ispartof>Journal of controlled release, 2010-03, Vol.142 (2), p.245-250</ispartof><rights>Copyright 2009 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19883708$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Suzuki, Ryo</creatorcontrib><creatorcontrib>Namai, Eisuke</creatorcontrib><creatorcontrib>Oda, Yusuke</creatorcontrib><creatorcontrib>Nishiie, Norihito</creatorcontrib><creatorcontrib>Otake, Shota</creatorcontrib><creatorcontrib>Koshima, Risa</creatorcontrib><creatorcontrib>Hirata, Keiichi</creatorcontrib><creatorcontrib>Taira, Yuichiro</creatorcontrib><creatorcontrib>Utoguchi, Naoki</creatorcontrib><creatorcontrib>Negishi, Yoichi</creatorcontrib><creatorcontrib>Nakagawa, Shinsaku</creatorcontrib><creatorcontrib>Maruyama, Kazuo</creatorcontrib><title>Cancer gene therapy by IL-12 gene delivery using liposomal bubbles and tumoral ultrasound exposure</title><title>Journal of controlled release</title><addtitle>J Control Release</addtitle><description>Interleukin-12 (IL-12) gene therapy is expected to be effective against cancers because it primes the immune system for cancer cells. In this therapy, it is important to induce IL-12 gene expression in the tumor tissue. Sonoporation is an attractive technique for developing non-invasive and non-viral gene delivery systems, but simple sonoporation using only ultrasound is not an effective cancer gene therapy because of the low efficiency of gene delivery. We addressed this problem by combining ultrasound and novel ultrasound-sensitive liposomes (Bubble liposomes) which contain the ultrasound imaging gas perfluoropropane. Our previous work showed that this is an effective gene delivery system, and that Bubble liposome collapse (cavitation) is induced by ultrasound exposure. In this study, we assessed the utility of this system in cancer gene therapy using IL-12 corded plasmid DNA. The combination of Bubble liposomes and ultrasound dramatically suppressed tumor growth. This therapeutic effect was T-cell dependent, requiring mainly CD8(+) T lymphocytes in the effector phase, as confirmed by a mouse in vivo depletion assay. In addition, migration of CD8(+) T cells was observed in the mice, indicating that the combination of Bubble liposomes and ultrasound is a good non-viral vector system in IL-12 cancer gene therapy.</description><subject>Animals</subject><subject>Cancer</subject><subject>Carcinoma - therapy</subject><subject>Cavitation</subject><subject>CD8 antigen</subject><subject>Controlled release</subject><subject>DNA</subject><subject>DNA - administration & dosage</subject><subject>Expression vectors</subject><subject>Female</subject><subject>Gene Expression</subject><subject>Gene therapy</subject><subject>Gene transfer</subject><subject>Gene Transfer Techniques</subject><subject>Genetic Therapy - methods</subject><subject>imaging</subject><subject>Immune system</subject><subject>Interleukin 12</subject><subject>Interleukin-12 - genetics</subject><subject>Leukocyte migration</subject><subject>Liposomes</subject><subject>Liposomes - chemistry</subject><subject>Lymphocytes T</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>Ovarian Neoplasms - therapy</subject><subject>Plasmids</subject><subject>Plasmids - administration & dosage</subject><subject>Transfection</subject><subject>Tumors</subject><subject>Ultrasonics</subject><subject>Ultrasound</subject><issn>0168-3659</issn><issn>1873-4995</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kEtLxDAUhYMozjj6E5TsdNOaNGnSLGXwMTDgRtclSe-MHdKHSSP23xsY3bo68PFxuecgdE1JTgkV94f8YIfeg8sLQlRiOSnkCVrSSrKMK1WeomXyqoyJUi3QRQgHQkjJuDxHC6qqiklSLZFZ696Cx3voAU8f4PU4YzPjzTajxZE24Nov8DOOoe332LXjEIZOO2yiMQ4C1n2Dp9gNPrHoJq_DEBOC7yRGD5fobKddgKvfXKH3p8e39Uu2fX3erB-22VhwNmXcGtU03ErbpDcNoVRwKTkoRq21hkjYESUULwXfKaMMpVJIQ2wqTBtaGbZCt8e7ox8-I4Sp7tpgwTndwxBDLRljQomKJvPuXzMNzCmRXJRJvflVo-mgqUffdtrP9d-C7AdR23UF</recordid><startdate>20100303</startdate><enddate>20100303</enddate><creator>Suzuki, Ryo</creator><creator>Namai, Eisuke</creator><creator>Oda, Yusuke</creator><creator>Nishiie, Norihito</creator><creator>Otake, Shota</creator><creator>Koshima, Risa</creator><creator>Hirata, Keiichi</creator><creator>Taira, Yuichiro</creator><creator>Utoguchi, Naoki</creator><creator>Negishi, Yoichi</creator><creator>Nakagawa, Shinsaku</creator><creator>Maruyama, Kazuo</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20100303</creationdate><title>Cancer gene therapy by IL-12 gene delivery using liposomal bubbles and tumoral ultrasound exposure</title><author>Suzuki, Ryo ; Namai, Eisuke ; Oda, Yusuke ; Nishiie, Norihito ; Otake, Shota ; Koshima, Risa ; Hirata, Keiichi ; Taira, Yuichiro ; Utoguchi, Naoki ; Negishi, Yoichi ; Nakagawa, Shinsaku ; Maruyama, Kazuo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p243t-4cb9dd4c7cd053b01164774e931cccb07ef09694564f9b9b11767b0c1871d18b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Animals</topic><topic>Cancer</topic><topic>Carcinoma - therapy</topic><topic>Cavitation</topic><topic>CD8 antigen</topic><topic>Controlled release</topic><topic>DNA</topic><topic>DNA - administration & dosage</topic><topic>Expression vectors</topic><topic>Female</topic><topic>Gene Expression</topic><topic>Gene therapy</topic><topic>Gene transfer</topic><topic>Gene Transfer Techniques</topic><topic>Genetic Therapy - methods</topic><topic>imaging</topic><topic>Immune system</topic><topic>Interleukin 12</topic><topic>Interleukin-12 - genetics</topic><topic>Leukocyte migration</topic><topic>Liposomes</topic><topic>Liposomes - chemistry</topic><topic>Lymphocytes T</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Nude</topic><topic>Ovarian Neoplasms - therapy</topic><topic>Plasmids</topic><topic>Plasmids - administration & dosage</topic><topic>Transfection</topic><topic>Tumors</topic><topic>Ultrasonics</topic><topic>Ultrasound</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Suzuki, Ryo</creatorcontrib><creatorcontrib>Namai, Eisuke</creatorcontrib><creatorcontrib>Oda, Yusuke</creatorcontrib><creatorcontrib>Nishiie, Norihito</creatorcontrib><creatorcontrib>Otake, Shota</creatorcontrib><creatorcontrib>Koshima, Risa</creatorcontrib><creatorcontrib>Hirata, Keiichi</creatorcontrib><creatorcontrib>Taira, Yuichiro</creatorcontrib><creatorcontrib>Utoguchi, Naoki</creatorcontrib><creatorcontrib>Negishi, Yoichi</creatorcontrib><creatorcontrib>Nakagawa, Shinsaku</creatorcontrib><creatorcontrib>Maruyama, Kazuo</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of controlled release</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Suzuki, Ryo</au><au>Namai, Eisuke</au><au>Oda, Yusuke</au><au>Nishiie, Norihito</au><au>Otake, Shota</au><au>Koshima, Risa</au><au>Hirata, Keiichi</au><au>Taira, Yuichiro</au><au>Utoguchi, Naoki</au><au>Negishi, Yoichi</au><au>Nakagawa, Shinsaku</au><au>Maruyama, Kazuo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cancer gene therapy by IL-12 gene delivery using liposomal bubbles and tumoral ultrasound exposure</atitle><jtitle>Journal of controlled release</jtitle><addtitle>J Control Release</addtitle><date>2010-03-03</date><risdate>2010</risdate><volume>142</volume><issue>2</issue><spage>245</spage><epage>250</epage><pages>245-250</pages><issn>0168-3659</issn><eissn>1873-4995</eissn><abstract>Interleukin-12 (IL-12) gene therapy is expected to be effective against cancers because it primes the immune system for cancer cells. In this therapy, it is important to induce IL-12 gene expression in the tumor tissue. Sonoporation is an attractive technique for developing non-invasive and non-viral gene delivery systems, but simple sonoporation using only ultrasound is not an effective cancer gene therapy because of the low efficiency of gene delivery. We addressed this problem by combining ultrasound and novel ultrasound-sensitive liposomes (Bubble liposomes) which contain the ultrasound imaging gas perfluoropropane. Our previous work showed that this is an effective gene delivery system, and that Bubble liposome collapse (cavitation) is induced by ultrasound exposure. In this study, we assessed the utility of this system in cancer gene therapy using IL-12 corded plasmid DNA. The combination of Bubble liposomes and ultrasound dramatically suppressed tumor growth. This therapeutic effect was T-cell dependent, requiring mainly CD8(+) T lymphocytes in the effector phase, as confirmed by a mouse in vivo depletion assay. In addition, migration of CD8(+) T cells was observed in the mice, indicating that the combination of Bubble liposomes and ultrasound is a good non-viral vector system in IL-12 cancer gene therapy.</abstract><cop>Netherlands</cop><pmid>19883708</pmid><doi>10.1016/j.jconrel.2009.10.027</doi><tpages>6</tpages></addata></record> |
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| ispartof | Journal of controlled release, 2010-03, Vol.142 (2), p.245-250 |
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| subjects | Animals Cancer Carcinoma - therapy Cavitation CD8 antigen Controlled release DNA DNA - administration & dosage Expression vectors Female Gene Expression Gene therapy Gene transfer Gene Transfer Techniques Genetic Therapy - methods imaging Immune system Interleukin 12 Interleukin-12 - genetics Leukocyte migration Liposomes Liposomes - chemistry Lymphocytes T Mice Mice, Inbred BALB C Mice, Nude Ovarian Neoplasms - therapy Plasmids Plasmids - administration & dosage Transfection Tumors Ultrasonics Ultrasound |
| title | Cancer gene therapy by IL-12 gene delivery using liposomal bubbles and tumoral ultrasound exposure |
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