Reducible poly(amido ethylenimine) directed to enhance RNA interference
Abstract Designing synthetic macromolecular vehicles with high transfection efficiency and low cytotoxicity has been a major interest in the development of non-viral gene carriers. A reducible poly(amido ethylenimine) (SS-PAEI) synthesized by addition copolymerization of triethylenetetramine and cys...
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| Veröffentlicht in: | Biomaterials 2007-04, Vol.28 (10), p.1912-1917 |
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| container_title | Biomaterials |
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| creator | Hoon Jeong, Ji Christensen, Lane V Yockman, James W Zhong, Zhiyuan Engbersen, Johan F.J Jong Kim, Won Feijen, Jan Wan Kim, Sung |
| description | Abstract Designing synthetic macromolecular vehicles with high transfection efficiency and low cytotoxicity has been a major interest in the development of non-viral gene carriers. A reducible poly(amido ethylenimine) (SS-PAEI) synthesized by addition copolymerization of triethylenetetramine and cystamine bis-acrylamide (poly(TETA/CBA)) was used as a carrier for small interference RNA (siRNA). Poly(TETA/CBA) could efficiently condense siRNA to form stable complexes under physiological conditions and perform complete release of siRNA in a reductive environment. When formulated with VEGF-directed siRNA, poly(TETA/CBA) demonstrated significantly higher suppression of VEGF than linear-polyethylenimine (PEI) (L-PEI, 25 kDa) in human prostate cancer cells (PC-3). After 5 h of transfection, substantial dissociation and intracellular distribution of siRNA was observed in the poly(TETA/CBA) formulation, but not in the L-PEI formulation. The triggered release of siRNA by reductive degradation of poly(TETA/CBA) in the cytoplasm may affect the RNAi activity by increasing cytoplasmic availability of siRNA. These results suggest that the rational design of non-viral carriers should involve considerations for intracellular dissociation and trafficking of a nucleic acid drug to maximize its effect, in conjunction with formation of stable complexes under physiological conditions. |
| doi_str_mv | 10.1016/j.biomaterials.2006.12.019 |
| format | Article |
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A reducible poly(amido ethylenimine) (SS-PAEI) synthesized by addition copolymerization of triethylenetetramine and cystamine bis-acrylamide (poly(TETA/CBA)) was used as a carrier for small interference RNA (siRNA). Poly(TETA/CBA) could efficiently condense siRNA to form stable complexes under physiological conditions and perform complete release of siRNA in a reductive environment. When formulated with VEGF-directed siRNA, poly(TETA/CBA) demonstrated significantly higher suppression of VEGF than linear-polyethylenimine (PEI) (L-PEI, 25 kDa) in human prostate cancer cells (PC-3). After 5 h of transfection, substantial dissociation and intracellular distribution of siRNA was observed in the poly(TETA/CBA) formulation, but not in the L-PEI formulation. The triggered release of siRNA by reductive degradation of poly(TETA/CBA) in the cytoplasm may affect the RNAi activity by increasing cytoplasmic availability of siRNA. These results suggest that the rational design of non-viral carriers should involve considerations for intracellular dissociation and trafficking of a nucleic acid drug to maximize its effect, in conjunction with formation of stable complexes under physiological conditions.</description><identifier>ISSN: 0142-9612</identifier><identifier>EISSN: 1878-5905</identifier><identifier>DOI: 10.1016/j.biomaterials.2006.12.019</identifier><identifier>PMID: 17218006</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Advanced Basic Science ; Aziridines - chemistry ; Cell Line, Tumor ; Dentistry ; Drug Carriers - chemistry ; Humans ; Male ; Materials Testing ; Non-viral gene delivery ; Poly(amido ethylenimine) ; Prostatic Neoplasms - genetics ; Prostatic Neoplasms - metabolism ; Reducible polymer ; RNA Interference ; RNA, Small Interfering - administration & dosage ; RNA, Small Interfering - chemistry ; RNA, Small Interfering - genetics ; RNA, Small Interfering - pharmacokinetics ; siRNA ; Transfection - methods</subject><ispartof>Biomaterials, 2007-04, Vol.28 (10), p.1912-1917</ispartof><rights>Elsevier Ltd</rights><rights>2006 Elsevier Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c495t-8e754e77ac3f562654ab1404c488a3d9ac0b17866bcff80ed68254241420ce283</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S014296120601026X$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17218006$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hoon Jeong, Ji</creatorcontrib><creatorcontrib>Christensen, Lane V</creatorcontrib><creatorcontrib>Yockman, James W</creatorcontrib><creatorcontrib>Zhong, Zhiyuan</creatorcontrib><creatorcontrib>Engbersen, Johan F.J</creatorcontrib><creatorcontrib>Jong Kim, Won</creatorcontrib><creatorcontrib>Feijen, Jan</creatorcontrib><creatorcontrib>Wan Kim, Sung</creatorcontrib><title>Reducible poly(amido ethylenimine) directed to enhance RNA interference</title><title>Biomaterials</title><addtitle>Biomaterials</addtitle><description>Abstract Designing synthetic macromolecular vehicles with high transfection efficiency and low cytotoxicity has been a major interest in the development of non-viral gene carriers. A reducible poly(amido ethylenimine) (SS-PAEI) synthesized by addition copolymerization of triethylenetetramine and cystamine bis-acrylamide (poly(TETA/CBA)) was used as a carrier for small interference RNA (siRNA). Poly(TETA/CBA) could efficiently condense siRNA to form stable complexes under physiological conditions and perform complete release of siRNA in a reductive environment. When formulated with VEGF-directed siRNA, poly(TETA/CBA) demonstrated significantly higher suppression of VEGF than linear-polyethylenimine (PEI) (L-PEI, 25 kDa) in human prostate cancer cells (PC-3). After 5 h of transfection, substantial dissociation and intracellular distribution of siRNA was observed in the poly(TETA/CBA) formulation, but not in the L-PEI formulation. The triggered release of siRNA by reductive degradation of poly(TETA/CBA) in the cytoplasm may affect the RNAi activity by increasing cytoplasmic availability of siRNA. These results suggest that the rational design of non-viral carriers should involve considerations for intracellular dissociation and trafficking of a nucleic acid drug to maximize its effect, in conjunction with formation of stable complexes under physiological conditions.</description><subject>Advanced Basic Science</subject><subject>Aziridines - chemistry</subject><subject>Cell Line, Tumor</subject><subject>Dentistry</subject><subject>Drug Carriers - chemistry</subject><subject>Humans</subject><subject>Male</subject><subject>Materials Testing</subject><subject>Non-viral gene delivery</subject><subject>Poly(amido ethylenimine)</subject><subject>Prostatic Neoplasms - genetics</subject><subject>Prostatic Neoplasms - metabolism</subject><subject>Reducible polymer</subject><subject>RNA Interference</subject><subject>RNA, Small Interfering - administration & dosage</subject><subject>RNA, Small Interfering - chemistry</subject><subject>RNA, Small Interfering - genetics</subject><subject>RNA, Small Interfering - pharmacokinetics</subject><subject>siRNA</subject><subject>Transfection - methods</subject><issn>0142-9612</issn><issn>1878-5905</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNUk1r3DAQFaWl2ab9C8HkUNKDnZFsffVQCEmbBkIKaQu5CVkeE238sZXswv77yOxCQi_pSUjz3szTe0PIMYWCAhWn66L2Y28nDN52sWAAoqCsAKpfkRVVUuVcA39NVkArlmtB2QF5F-Ma0h0q9pYcUMmoSrQVubzFZna-7jDbjN32xPa-GTOc7rcdDr73A37KGh_QTdhkU6oM93ZwmN3enGV-SBJaDJge3pM3bRKDH_bnIfn97euv8-_59Y_Lq_Oz69xVmk-5QskrlNK6suWCCV7ZehHlKqVs2WjroKZSCVG7tlWAjVCMV6xKHwGHTJWH5OOu7yaMf2aMk-l9dNh1dsBxjkYozUEr_iKQaS6VBP0ikGoltVZlAn7eAV0YYwzYmk3wvQ1bQ8EswZi1eR6MWYIxlJkUTCIf7afMdY_NE3WfRAJc7ACY3PvrMZjo_OLszn3TjP7_5nz5p43r_OCd7R5wi3E9zmFYONTERDA_lxVZNgQEUGDirnwEvDy5vg</recordid><startdate>20070401</startdate><enddate>20070401</enddate><creator>Hoon Jeong, Ji</creator><creator>Christensen, Lane V</creator><creator>Yockman, James W</creator><creator>Zhong, Zhiyuan</creator><creator>Engbersen, Johan F.J</creator><creator>Jong Kim, Won</creator><creator>Feijen, Jan</creator><creator>Wan Kim, Sung</creator><general>Elsevier Ltd</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>7QO</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7SR</scope><scope>7TB</scope><scope>7U5</scope><scope>8BQ</scope><scope>F28</scope><scope>JG9</scope><scope>L7M</scope><scope>7X8</scope></search><sort><creationdate>20070401</creationdate><title>Reducible poly(amido ethylenimine) directed to enhance RNA interference</title><author>Hoon Jeong, Ji ; Christensen, Lane V ; Yockman, James W ; Zhong, Zhiyuan ; Engbersen, Johan F.J ; Jong Kim, Won ; Feijen, Jan ; Wan Kim, Sung</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c495t-8e754e77ac3f562654ab1404c488a3d9ac0b17866bcff80ed68254241420ce283</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Advanced Basic Science</topic><topic>Aziridines - chemistry</topic><topic>Cell Line, Tumor</topic><topic>Dentistry</topic><topic>Drug Carriers - chemistry</topic><topic>Humans</topic><topic>Male</topic><topic>Materials Testing</topic><topic>Non-viral gene delivery</topic><topic>Poly(amido ethylenimine)</topic><topic>Prostatic Neoplasms - genetics</topic><topic>Prostatic Neoplasms - metabolism</topic><topic>Reducible polymer</topic><topic>RNA Interference</topic><topic>RNA, Small Interfering - administration & dosage</topic><topic>RNA, Small Interfering - chemistry</topic><topic>RNA, Small Interfering - genetics</topic><topic>RNA, Small Interfering - pharmacokinetics</topic><topic>siRNA</topic><topic>Transfection - methods</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hoon Jeong, Ji</creatorcontrib><creatorcontrib>Christensen, Lane V</creatorcontrib><creatorcontrib>Yockman, James W</creatorcontrib><creatorcontrib>Zhong, Zhiyuan</creatorcontrib><creatorcontrib>Engbersen, Johan F.J</creatorcontrib><creatorcontrib>Jong Kim, Won</creatorcontrib><creatorcontrib>Feijen, Jan</creatorcontrib><creatorcontrib>Wan Kim, Sung</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Materials Research Database</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>MEDLINE - Academic</collection><jtitle>Biomaterials</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hoon Jeong, Ji</au><au>Christensen, Lane V</au><au>Yockman, James W</au><au>Zhong, Zhiyuan</au><au>Engbersen, Johan F.J</au><au>Jong Kim, Won</au><au>Feijen, Jan</au><au>Wan Kim, Sung</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Reducible poly(amido ethylenimine) directed to enhance RNA interference</atitle><jtitle>Biomaterials</jtitle><addtitle>Biomaterials</addtitle><date>2007-04-01</date><risdate>2007</risdate><volume>28</volume><issue>10</issue><spage>1912</spage><epage>1917</epage><pages>1912-1917</pages><issn>0142-9612</issn><eissn>1878-5905</eissn><abstract>Abstract Designing synthetic macromolecular vehicles with high transfection efficiency and low cytotoxicity has been a major interest in the development of non-viral gene carriers. A reducible poly(amido ethylenimine) (SS-PAEI) synthesized by addition copolymerization of triethylenetetramine and cystamine bis-acrylamide (poly(TETA/CBA)) was used as a carrier for small interference RNA (siRNA). Poly(TETA/CBA) could efficiently condense siRNA to form stable complexes under physiological conditions and perform complete release of siRNA in a reductive environment. When formulated with VEGF-directed siRNA, poly(TETA/CBA) demonstrated significantly higher suppression of VEGF than linear-polyethylenimine (PEI) (L-PEI, 25 kDa) in human prostate cancer cells (PC-3). After 5 h of transfection, substantial dissociation and intracellular distribution of siRNA was observed in the poly(TETA/CBA) formulation, but not in the L-PEI formulation. The triggered release of siRNA by reductive degradation of poly(TETA/CBA) in the cytoplasm may affect the RNAi activity by increasing cytoplasmic availability of siRNA. 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| subjects | Advanced Basic Science Aziridines - chemistry Cell Line, Tumor Dentistry Drug Carriers - chemistry Humans Male Materials Testing Non-viral gene delivery Poly(amido ethylenimine) Prostatic Neoplasms - genetics Prostatic Neoplasms - metabolism Reducible polymer RNA Interference RNA, Small Interfering - administration & dosage RNA, Small Interfering - chemistry RNA, Small Interfering - genetics RNA, Small Interfering - pharmacokinetics siRNA Transfection - methods |
| title | Reducible poly(amido ethylenimine) directed to enhance RNA interference |
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