Enhanced Intrapulmonary Delivery of Anticancer siRNA for Lung Cancer Therapy Using Cationic Ethylphosphocholine-based Nanolipoplexes
Here, we report a cationic nanolipoplex as a pulmonary cellular delivery system for small-interfering RNA (siRNA). Six nanoliposomes differing in cationic lipids were formulated and screened in vitro and in vivo for cellular delivery functions in lung cells/tissues. Although the six nanoliposomes sh...
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| Veröffentlicht in: | Molecular therapy 2013-04, Vol.21 (4), p.816-824 |
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| container_title | Molecular therapy |
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| creator | Shim, Gayong Choi, Hyun-woo Lee, Sangbin Choi, Junhyeok Yu, Yong Hee Park, Da-Eui Choi, Yongseok Kim, Chan-Wha Oh, Yu-Kyoung |
| description | Here, we report a cationic nanolipoplex as a pulmonary cellular delivery system for small-interfering RNA (siRNA). Six nanoliposomes differing in cationic lipids were formulated and screened in vitro and in vivo for cellular delivery functions in lung cells/tissues. Although the six nanoliposomes showed similar siRNA delivery efficiency in vitro, they exhibited significant differences in pulmonary cellular delivery functions in vivo. Among the various nanoliposomes, cationic dioleoyl-sn-glycero-3-ethylphosphocholine and cholesterol (ECL)-based nanoliposomes showed the highest pulmonary cellular delivery in vivo and the lowest cytotoxicity in vitro. The delivery efficiency of fluorescent siRNA in ECL nanoliposomes was 26.2-fold higher than that of naked siRNA in vivo. Treatment with Mcl1 (myeloid cell leukemia sequence 1)-specific siRNA (siMcl1) using ECL nanolipoplexes reduced target expression in B16F10 cell lines, whereas control, luciferase-specific siGL2 in ECL nanolipoplexes did not. In metastatic lung cancer mouse models induced by B16F10 or Lewis lung carcinoma (LLC) cells, intratracheal administration of siMcl1 in ECL nanolipoplexes significantly silenced Mcl1 mRNA and protein levels in lung tissue. Reduced formation of melanoma tumor nodules was observed in the lung. These results demonstrate the utility of ECL nanoliposomes for pulmonary delivery of therapeutic siRNA for the treatment of lung cancers and potentially for other respiratory diseases. |
| doi_str_mv | 10.1038/mt.2013.10 |
| format | Article |
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Six nanoliposomes differing in cationic lipids were formulated and screened in vitro and in vivo for cellular delivery functions in lung cells/tissues. Although the six nanoliposomes showed similar siRNA delivery efficiency in vitro, they exhibited significant differences in pulmonary cellular delivery functions in vivo. Among the various nanoliposomes, cationic dioleoyl-sn-glycero-3-ethylphosphocholine and cholesterol (ECL)-based nanoliposomes showed the highest pulmonary cellular delivery in vivo and the lowest cytotoxicity in vitro. The delivery efficiency of fluorescent siRNA in ECL nanoliposomes was 26.2-fold higher than that of naked siRNA in vivo. Treatment with Mcl1 (myeloid cell leukemia sequence 1)-specific siRNA (siMcl1) using ECL nanolipoplexes reduced target expression in B16F10 cell lines, whereas control, luciferase-specific siGL2 in ECL nanolipoplexes did not. In metastatic lung cancer mouse models induced by B16F10 or Lewis lung carcinoma (LLC) cells, intratracheal administration of siMcl1 in ECL nanolipoplexes significantly silenced Mcl1 mRNA and protein levels in lung tissue. Reduced formation of melanoma tumor nodules was observed in the lung. These results demonstrate the utility of ECL nanoliposomes for pulmonary delivery of therapeutic siRNA for the treatment of lung cancers and potentially for other respiratory diseases.</description><identifier>ISSN: 1525-0016</identifier><identifier>EISSN: 1525-0024</identifier><identifier>DOI: 10.1038/mt.2013.10</identifier><identifier>PMID: 23380818</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Blotting, Western ; Cell Line, Tumor ; Female ; Flow Cytometry ; Liposomes - chemistry ; Lung - metabolism ; Lung - pathology ; Lung cancer ; Lung Neoplasms - therapy ; Mice ; Mice, Inbred BALB C ; Original ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Small Interfering - genetics ; RNA, Small Interfering - therapeutic use</subject><ispartof>Molecular therapy, 2013-04, Vol.21 (4), p.816-824</ispartof><rights>2013 The American Society of Gene & Cell Therapy</rights><rights>Copyright Nature Publishing Group Apr 2013</rights><rights>Copyright © 2013 The American Society of Gene & Cell Therapy 2013 The American Society of Gene & Cell Therapy</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c550t-e40e32fe701921cbd9ae4c03b4aa1dd606616aa4cfb002fa4dd2fbf318e67a103</citedby><cites>FETCH-LOGICAL-c550t-e40e32fe701921cbd9ae4c03b4aa1dd606616aa4cfb002fa4dd2fbf318e67a103</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3616525/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3616525/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23380818$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shim, Gayong</creatorcontrib><creatorcontrib>Choi, Hyun-woo</creatorcontrib><creatorcontrib>Lee, Sangbin</creatorcontrib><creatorcontrib>Choi, Junhyeok</creatorcontrib><creatorcontrib>Yu, Yong Hee</creatorcontrib><creatorcontrib>Park, Da-Eui</creatorcontrib><creatorcontrib>Choi, Yongseok</creatorcontrib><creatorcontrib>Kim, Chan-Wha</creatorcontrib><creatorcontrib>Oh, Yu-Kyoung</creatorcontrib><title>Enhanced Intrapulmonary Delivery of Anticancer siRNA for Lung Cancer Therapy Using Cationic Ethylphosphocholine-based Nanolipoplexes</title><title>Molecular therapy</title><addtitle>Mol Ther</addtitle><description>Here, we report a cationic nanolipoplex as a pulmonary cellular delivery system for small-interfering RNA (siRNA). Six nanoliposomes differing in cationic lipids were formulated and screened in vitro and in vivo for cellular delivery functions in lung cells/tissues. Although the six nanoliposomes showed similar siRNA delivery efficiency in vitro, they exhibited significant differences in pulmonary cellular delivery functions in vivo. Among the various nanoliposomes, cationic dioleoyl-sn-glycero-3-ethylphosphocholine and cholesterol (ECL)-based nanoliposomes showed the highest pulmonary cellular delivery in vivo and the lowest cytotoxicity in vitro. The delivery efficiency of fluorescent siRNA in ECL nanoliposomes was 26.2-fold higher than that of naked siRNA in vivo. Treatment with Mcl1 (myeloid cell leukemia sequence 1)-specific siRNA (siMcl1) using ECL nanolipoplexes reduced target expression in B16F10 cell lines, whereas control, luciferase-specific siGL2 in ECL nanolipoplexes did not. In metastatic lung cancer mouse models induced by B16F10 or Lewis lung carcinoma (LLC) cells, intratracheal administration of siMcl1 in ECL nanolipoplexes significantly silenced Mcl1 mRNA and protein levels in lung tissue. Reduced formation of melanoma tumor nodules was observed in the lung. These results demonstrate the utility of ECL nanoliposomes for pulmonary delivery of therapeutic siRNA for the treatment of lung cancers and potentially for other respiratory diseases.</description><subject>Animals</subject><subject>Blotting, Western</subject><subject>Cell Line, Tumor</subject><subject>Female</subject><subject>Flow Cytometry</subject><subject>Liposomes - chemistry</subject><subject>Lung - metabolism</subject><subject>Lung - pathology</subject><subject>Lung cancer</subject><subject>Lung Neoplasms - therapy</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Original</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Small Interfering - genetics</subject><subject>RNA, Small Interfering - therapeutic use</subject><issn>1525-0016</issn><issn>1525-0024</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqFkl2L1DAUhoso7rp64w-Qgjey0DUfbZreCMM46sKwguxehzQ92WZpk5qkg3PvD990Zx1UBC9CzkmevMl5c7LsNUYXGFH-fowXBGGakifZKa5IVSBEyqfHGLOT7EUIdynCVcOeZyeEUo445qfZz43tpVXQ5Zc2ejnNw-is9Pv8IwxmBylwOl_ZaNRC-TyYb1erXDufb2d7m68Pq9c9pLP7_CaYh8VonDUq38R-P0y9C2mo3g3GQtHKkC67kjalk5sG-AHhZfZMyyHAq8f5LLv5tLlefym2Xz9frlfbQlUVigWUCCjRUCPcEKzarpFQKkTbUkrcdQwxhpmUpdJtMkDLsuuIbjXFHFgtk1Vn2YeD7jS3I3QKlpIHMXkzppKFk0b8uWNNL27dTtAknLxMAu8eBbz7PkOIYjRBwTBIC24OAjPGCeO8Qv9HKSE1JbzhCX37F3rnZm-TEwLXDea8RmWdqPMDpbwLwYM-vhsjsfSBGKNY-kA8VPrm90qP6K-PT0B5ACD5vTPgRVAGlkYwHlQUnTP_0r0HD9rCjw</recordid><startdate>20130401</startdate><enddate>20130401</enddate><creator>Shim, Gayong</creator><creator>Choi, Hyun-woo</creator><creator>Lee, Sangbin</creator><creator>Choi, Junhyeok</creator><creator>Yu, Yong Hee</creator><creator>Park, Da-Eui</creator><creator>Choi, Yongseok</creator><creator>Kim, Chan-Wha</creator><creator>Oh, Yu-Kyoung</creator><general>Elsevier Inc</general><general>Elsevier Limited</general><general>Nature Publishing Group</general><scope>6I.</scope><scope>AAFTH</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>7QO</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>5PM</scope></search><sort><creationdate>20130401</creationdate><title>Enhanced Intrapulmonary Delivery of Anticancer siRNA for Lung Cancer Therapy Using Cationic Ethylphosphocholine-based Nanolipoplexes</title><author>Shim, Gayong ; 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Six nanoliposomes differing in cationic lipids were formulated and screened in vitro and in vivo for cellular delivery functions in lung cells/tissues. Although the six nanoliposomes showed similar siRNA delivery efficiency in vitro, they exhibited significant differences in pulmonary cellular delivery functions in vivo. Among the various nanoliposomes, cationic dioleoyl-sn-glycero-3-ethylphosphocholine and cholesterol (ECL)-based nanoliposomes showed the highest pulmonary cellular delivery in vivo and the lowest cytotoxicity in vitro. The delivery efficiency of fluorescent siRNA in ECL nanoliposomes was 26.2-fold higher than that of naked siRNA in vivo. Treatment with Mcl1 (myeloid cell leukemia sequence 1)-specific siRNA (siMcl1) using ECL nanolipoplexes reduced target expression in B16F10 cell lines, whereas control, luciferase-specific siGL2 in ECL nanolipoplexes did not. In metastatic lung cancer mouse models induced by B16F10 or Lewis lung carcinoma (LLC) cells, intratracheal administration of siMcl1 in ECL nanolipoplexes significantly silenced Mcl1 mRNA and protein levels in lung tissue. Reduced formation of melanoma tumor nodules was observed in the lung. These results demonstrate the utility of ECL nanoliposomes for pulmonary delivery of therapeutic siRNA for the treatment of lung cancers and potentially for other respiratory diseases.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>23380818</pmid><doi>10.1038/mt.2013.10</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Blotting, Western Cell Line, Tumor Female Flow Cytometry Liposomes - chemistry Lung - metabolism Lung - pathology Lung cancer Lung Neoplasms - therapy Mice Mice, Inbred BALB C Original Real-Time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction RNA, Small Interfering - genetics RNA, Small Interfering - therapeutic use |
| title | Enhanced Intrapulmonary Delivery of Anticancer siRNA for Lung Cancer Therapy Using Cationic Ethylphosphocholine-based Nanolipoplexes |
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