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Chitosan hydrogel for localized gene silencing
Objective: To achieve effective delivery of siRNA into target cells in vivo, we have developed a novel approach of siRNA delivery by using local drug delivery systems. Results: The chitosan hydrogel (CH-HG) displayed a liquid-solid phase transition in a temperature-dependent manner and formed an end...
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| Published in: | Cancer biology & therapy 2011-05, Vol.11 (9), p.839-845 |
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| Main Authors: | , , , , , , , , |
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| cites | cdi_FETCH-LOGICAL-c522t-72b4e5e285b21e4124f9d11e4ec27abd1d49b13b1bab77e261537ae798a99683 |
| container_end_page | 845 |
| container_issue | 9 |
| container_start_page | 839 |
| container_title | Cancer biology & therapy |
| container_volume | 11 |
| creator | Han, Hee Dong Mora, Edna M. Roh, Ju Won Nishimura, Masato Lee, Sun Joo Stone, Rebecca L. Bar-Eli, Menashe Lopez-Berestein, Gabriel Sood, Anil K |
| description | Objective: To achieve effective delivery of siRNA into target cells in vivo, we have developed a novel approach of siRNA delivery by using local drug delivery systems.
Results: The chitosan hydrogel (CH-HG) displayed a liquid-solid phase transition in a temperature-dependent manner and formed an endothermic hydrogel in tumor tissue after intra-tumoral injection. Additionally, we tested the extent of in vivo delivery following a single intra-tumoral injection of Alexa555 siRNA/CH-HG into A375SM-bearing mice. The Alexa555 siRNA demonstrated higher localization into tumor cells compared to control. The Alexa555 siRNA delivery extends to tumor cells outside of CH-HG and some tumor cells also infiltrated into CH-HG. For therapeutic proof-of-concept studies, CH-HG including TG2-targeted siRNA significantly inhibited tumor growth in melanoma (A375SM) and breast (MDA-MB231) tumor models compared to control (A375SM: 72% reduction and MDA-MB231: 92% reduction, p |
| doi_str_mv | 10.4161/cbt.11.9.15185 |
| format | article |
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Results: The chitosan hydrogel (CH-HG) displayed a liquid-solid phase transition in a temperature-dependent manner and formed an endothermic hydrogel in tumor tissue after intra-tumoral injection. Additionally, we tested the extent of in vivo delivery following a single intra-tumoral injection of Alexa555 siRNA/CH-HG into A375SM-bearing mice. The Alexa555 siRNA demonstrated higher localization into tumor cells compared to control. The Alexa555 siRNA delivery extends to tumor cells outside of CH-HG and some tumor cells also infiltrated into CH-HG. For therapeutic proof-of-concept studies, CH-HG including TG2-targeted siRNA significantly inhibited tumor growth in melanoma (A375SM) and breast (MDA-MB231) tumor models compared to control (A375SM: 72% reduction and MDA-MB231: 92% reduction, p<0.001).
Experimental Design: we prepared a CH-HG system loaded with siRNA to enhance localized therapeutic efficacy without risk for systemic side effects. Delivery of siRNA into CH-HG was confirmed by fluorescence microscopy. Antitumor efficacy was examined in mouse models of melanoma (A375SM) and breast (MDA-MD231) cancer.
Conclusions: This study developed a novel local delivery method for siRNA therapy using the CH-HG system. This approach could have broad applications for multiple localized diseases.
See commentary:
Hydrogel-siRNA for cancer therapy</description><identifier>ISSN: 1538-4047</identifier><identifier>EISSN: 1555-8576</identifier><identifier>DOI: 10.4161/cbt.11.9.15185</identifier><identifier>PMID: 21358280</identifier><language>eng</language><publisher>United States: Taylor & Francis</publisher><subject>Animals ; Binding ; Biology ; Bioscience ; Breast Neoplasms - genetics ; Breast Neoplasms - therapy ; Calcium ; Cancer ; Cell ; Cell Line, Tumor ; Chitosan - administration & dosage ; Cycle ; Drug Delivery Systems - methods ; Female ; Gene Silencing ; Humans ; Hydrogels - administration & dosage ; Landes ; Melanoma - genetics ; Melanoma - therapy ; Mice ; Mice, Nude ; Organogenesis ; Proteins ; Research Paper ; RNA, Small Interfering - administration & dosage ; RNA, Small Interfering - genetics ; Xenograft Model Antitumor Assays</subject><ispartof>Cancer biology & therapy, 2011-05, Vol.11 (9), p.839-845</ispartof><rights>Copyright © 2011 Landes Bioscience 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c522t-72b4e5e285b21e4124f9d11e4ec27abd1d49b13b1bab77e261537ae798a99683</citedby><cites>FETCH-LOGICAL-c522t-72b4e5e285b21e4124f9d11e4ec27abd1d49b13b1bab77e261537ae798a99683</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/PMC3100632/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3100632/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21358280$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Han, Hee Dong</creatorcontrib><creatorcontrib>Mora, Edna M.</creatorcontrib><creatorcontrib>Roh, Ju Won</creatorcontrib><creatorcontrib>Nishimura, Masato</creatorcontrib><creatorcontrib>Lee, Sun Joo</creatorcontrib><creatorcontrib>Stone, Rebecca L.</creatorcontrib><creatorcontrib>Bar-Eli, Menashe</creatorcontrib><creatorcontrib>Lopez-Berestein, Gabriel</creatorcontrib><creatorcontrib>Sood, Anil K</creatorcontrib><title>Chitosan hydrogel for localized gene silencing</title><title>Cancer biology & therapy</title><addtitle>Cancer Biol Ther</addtitle><description>Objective: To achieve effective delivery of siRNA into target cells in vivo, we have developed a novel approach of siRNA delivery by using local drug delivery systems.
Results: The chitosan hydrogel (CH-HG) displayed a liquid-solid phase transition in a temperature-dependent manner and formed an endothermic hydrogel in tumor tissue after intra-tumoral injection. Additionally, we tested the extent of in vivo delivery following a single intra-tumoral injection of Alexa555 siRNA/CH-HG into A375SM-bearing mice. The Alexa555 siRNA demonstrated higher localization into tumor cells compared to control. The Alexa555 siRNA delivery extends to tumor cells outside of CH-HG and some tumor cells also infiltrated into CH-HG. For therapeutic proof-of-concept studies, CH-HG including TG2-targeted siRNA significantly inhibited tumor growth in melanoma (A375SM) and breast (MDA-MB231) tumor models compared to control (A375SM: 72% reduction and MDA-MB231: 92% reduction, p<0.001).
Experimental Design: we prepared a CH-HG system loaded with siRNA to enhance localized therapeutic efficacy without risk for systemic side effects. Delivery of siRNA into CH-HG was confirmed by fluorescence microscopy. Antitumor efficacy was examined in mouse models of melanoma (A375SM) and breast (MDA-MD231) cancer.
Conclusions: This study developed a novel local delivery method for siRNA therapy using the CH-HG system. This approach could have broad applications for multiple localized diseases.
See commentary:
Hydrogel-siRNA for cancer therapy</description><subject>Animals</subject><subject>Binding</subject><subject>Biology</subject><subject>Bioscience</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - therapy</subject><subject>Calcium</subject><subject>Cancer</subject><subject>Cell</subject><subject>Cell Line, Tumor</subject><subject>Chitosan - administration & dosage</subject><subject>Cycle</subject><subject>Drug Delivery Systems - methods</subject><subject>Female</subject><subject>Gene Silencing</subject><subject>Humans</subject><subject>Hydrogels - administration & dosage</subject><subject>Landes</subject><subject>Melanoma - genetics</subject><subject>Melanoma - therapy</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Organogenesis</subject><subject>Proteins</subject><subject>Research Paper</subject><subject>RNA, Small Interfering - administration & dosage</subject><subject>RNA, Small Interfering - genetics</subject><subject>Xenograft Model Antitumor Assays</subject><issn>1538-4047</issn><issn>1555-8576</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><recordid>eNqFkUFv1DAQhS1ERUvLlSPKjVOCx4lj-4IEK6BIlXrZu2U7k10jb7zYWdDy63G6ZQUSUk8eye89P39DyGugTQc9vHN2bgAa1QAHyZ-RK-Cc15KL_vkyt7LuaCcuycucv1HKBOvVC3LJoOWSSXpFmtXWzzGbqdoehxQ3GKoxpipEZ4L_hUO1wQmr7ANOzk-bG3IxmpDx1eN5TdafP61Xt_Xd_Zevqw93teOMzbVgtkOOTHLLADtg3agGKBM6JowdYOiUhdaCNVYIZH1pKgwKJY1SvWyvyftT7P5gdzg4nOZkgt4nvzPpqKPx-t-byW_1Jv7QLVDat6wEvH0MSPH7AfOsdz47DMFMGA9Zy74TkjO5KJuT0qWYc8Lx_ApQvSDWBbEG0Eo_IC6GN393O8v_MC0CehKUxwbM1sfsfMGHZykVt2ZafVw_pO6HsVjgCctSwqTZu4DnHurk8VPZ2M78jCkMejbHENOYTFlXXnD89w-_AQTtrtc</recordid><startdate>20110501</startdate><enddate>20110501</enddate><creator>Han, Hee Dong</creator><creator>Mora, Edna M.</creator><creator>Roh, Ju Won</creator><creator>Nishimura, Masato</creator><creator>Lee, Sun Joo</creator><creator>Stone, Rebecca L.</creator><creator>Bar-Eli, Menashe</creator><creator>Lopez-Berestein, Gabriel</creator><creator>Sood, Anil K</creator><general>Taylor & Francis</general><general>Landes Bioscience</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20110501</creationdate><title>Chitosan hydrogel for localized gene silencing</title><author>Han, Hee Dong ; Mora, Edna M. ; Roh, Ju Won ; Nishimura, Masato ; Lee, Sun Joo ; Stone, Rebecca L. ; Bar-Eli, Menashe ; Lopez-Berestein, Gabriel ; Sood, Anil K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c522t-72b4e5e285b21e4124f9d11e4ec27abd1d49b13b1bab77e261537ae798a99683</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Animals</topic><topic>Binding</topic><topic>Biology</topic><topic>Bioscience</topic><topic>Breast Neoplasms - genetics</topic><topic>Breast Neoplasms - therapy</topic><topic>Calcium</topic><topic>Cancer</topic><topic>Cell</topic><topic>Cell Line, Tumor</topic><topic>Chitosan - administration & dosage</topic><topic>Cycle</topic><topic>Drug Delivery Systems - methods</topic><topic>Female</topic><topic>Gene Silencing</topic><topic>Humans</topic><topic>Hydrogels - administration & dosage</topic><topic>Landes</topic><topic>Melanoma - genetics</topic><topic>Melanoma - therapy</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Organogenesis</topic><topic>Proteins</topic><topic>Research Paper</topic><topic>RNA, Small Interfering - administration & dosage</topic><topic>RNA, Small Interfering - genetics</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Han, Hee Dong</creatorcontrib><creatorcontrib>Mora, Edna M.</creatorcontrib><creatorcontrib>Roh, Ju Won</creatorcontrib><creatorcontrib>Nishimura, Masato</creatorcontrib><creatorcontrib>Lee, Sun Joo</creatorcontrib><creatorcontrib>Stone, Rebecca L.</creatorcontrib><creatorcontrib>Bar-Eli, Menashe</creatorcontrib><creatorcontrib>Lopez-Berestein, Gabriel</creatorcontrib><creatorcontrib>Sood, Anil K</creatorcontrib><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><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer biology & therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Han, Hee Dong</au><au>Mora, Edna M.</au><au>Roh, Ju Won</au><au>Nishimura, Masato</au><au>Lee, Sun Joo</au><au>Stone, Rebecca L.</au><au>Bar-Eli, Menashe</au><au>Lopez-Berestein, Gabriel</au><au>Sood, Anil K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Chitosan hydrogel for localized gene silencing</atitle><jtitle>Cancer biology & therapy</jtitle><addtitle>Cancer Biol Ther</addtitle><date>2011-05-01</date><risdate>2011</risdate><volume>11</volume><issue>9</issue><spage>839</spage><epage>845</epage><pages>839-845</pages><issn>1538-4047</issn><eissn>1555-8576</eissn><abstract>Objective: To achieve effective delivery of siRNA into target cells in vivo, we have developed a novel approach of siRNA delivery by using local drug delivery systems.
Results: The chitosan hydrogel (CH-HG) displayed a liquid-solid phase transition in a temperature-dependent manner and formed an endothermic hydrogel in tumor tissue after intra-tumoral injection. Additionally, we tested the extent of in vivo delivery following a single intra-tumoral injection of Alexa555 siRNA/CH-HG into A375SM-bearing mice. The Alexa555 siRNA demonstrated higher localization into tumor cells compared to control. The Alexa555 siRNA delivery extends to tumor cells outside of CH-HG and some tumor cells also infiltrated into CH-HG. For therapeutic proof-of-concept studies, CH-HG including TG2-targeted siRNA significantly inhibited tumor growth in melanoma (A375SM) and breast (MDA-MB231) tumor models compared to control (A375SM: 72% reduction and MDA-MB231: 92% reduction, p<0.001).
Experimental Design: we prepared a CH-HG system loaded with siRNA to enhance localized therapeutic efficacy without risk for systemic side effects. Delivery of siRNA into CH-HG was confirmed by fluorescence microscopy. Antitumor efficacy was examined in mouse models of melanoma (A375SM) and breast (MDA-MD231) cancer.
Conclusions: This study developed a novel local delivery method for siRNA therapy using the CH-HG system. This approach could have broad applications for multiple localized diseases.
See commentary:
Hydrogel-siRNA for cancer therapy</abstract><cop>United States</cop><pub>Taylor & Francis</pub><pmid>21358280</pmid><doi>10.4161/cbt.11.9.15185</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Cancer biology & therapy, 2011-05, Vol.11 (9), p.839-845 |
| issn | 1538-4047 1555-8576 |
| language | eng |
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| source | EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Animals Binding Biology Bioscience Breast Neoplasms - genetics Breast Neoplasms - therapy Calcium Cancer Cell Cell Line, Tumor Chitosan - administration & dosage Cycle Drug Delivery Systems - methods Female Gene Silencing Humans Hydrogels - administration & dosage Landes Melanoma - genetics Melanoma - therapy Mice Mice, Nude Organogenesis Proteins Research Paper RNA, Small Interfering - administration & dosage RNA, Small Interfering - genetics Xenograft Model Antitumor Assays |
| title | Chitosan hydrogel for localized gene silencing |
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