Delivery of Telomerase Reverse Transcriptase Small Interfering RNA in Complex with Positively Charged Single-Walled Carbon Nanotubes Suppresses Tumor Growth

Purpose: To determine whether -CONH-(CH 2 ) 6 -NH 3 + Cl − functionalized single-walled carbon nanotubes (SWNT) carrying complexed small interfering RNA (siRNA) can enter into tumor cells, wherein they release the siRNA to silence the targeted gene. Experimental Design: -CONH-(CH 2 ) 6 -NH 3 + Cl −...

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Veröffentlicht in:Clinical cancer research 2006-08, Vol.12 (16), p.4933-4939
Hauptverfasser: Zhang, Zhuohan, Yang, Xiaoying, Zhang, Yuan, Zeng, Bin, Wang, Shujing, Zhu, Tianhui, Roden, Richard B S, Chen, Yongsheng, Yang, Rongcun
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container_end_page 4939
container_issue 16
container_start_page 4933
container_title Clinical cancer research
container_volume 12
creator Zhang, Zhuohan
Yang, Xiaoying
Zhang, Yuan
Zeng, Bin
Wang, Shujing
Zhu, Tianhui
Roden, Richard B S
Chen, Yongsheng
Yang, Rongcun
description Purpose: To determine whether -CONH-(CH 2 ) 6 -NH 3 + Cl − functionalized single-walled carbon nanotubes (SWNT) carrying complexed small interfering RNA (siRNA) can enter into tumor cells, wherein they release the siRNA to silence the targeted gene. Experimental Design: -CONH-(CH 2 ) 6 -NH 3 + Cl − was used to mediate the conjugation of telomerase reverse transcriptase (TERT) siRNA to SWNTs. The ability of TERT siRNA delivered via SWNT complexes to silence the expression of TERT was assessed by their effects on the proliferation and growth of tumor cells both in vitro and in mouse models. Results: The functionalized SWNTs -CONH-(CH 2 ) 6 -NH 3 + Cl − could facilitate the coupling of siRNAs that specifically target murine TERT expression to form the mTERT siRNA:SWNT+ complex. These functionalized SWNTs rapidly entered three cultured murine tumor cell lines, suppressed mTERT expression, and produced growth arrest. Injection of mTERT siRNA:SWNT+ complexes into s.c. Lewis lung tumors reduced tumor growth. Furthermore, human TERT siRNA:SWNT+ complexes also suppressed the growth of human HeLa cells both in vitro and when injected into tumors in nude mice. Conclusions: -CONH-(CH 2 ) 6 -NH 3 + Cl − functionalized SWNTs carry complexed siRNA into tumor cells, wherein they release the siRNA from the nanotube sidewalls to silence the targeted gene. The -CONH-(CH 2 ) 6 -NH 3 + Cl − functionalized SWNTs may represent a new class of molecular transporters applicable for siRNA therapeutics.
doi_str_mv 10.1158/1078-0432.CCR-05-2831
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Experimental Design: -CONH-(CH 2 ) 6 -NH 3 + Cl − was used to mediate the conjugation of telomerase reverse transcriptase (TERT) siRNA to SWNTs. The ability of TERT siRNA delivered via SWNT complexes to silence the expression of TERT was assessed by their effects on the proliferation and growth of tumor cells both in vitro and in mouse models. Results: The functionalized SWNTs -CONH-(CH 2 ) 6 -NH 3 + Cl − could facilitate the coupling of siRNAs that specifically target murine TERT expression to form the mTERT siRNA:SWNT+ complex. These functionalized SWNTs rapidly entered three cultured murine tumor cell lines, suppressed mTERT expression, and produced growth arrest. Injection of mTERT siRNA:SWNT+ complexes into s.c. Lewis lung tumors reduced tumor growth. Furthermore, human TERT siRNA:SWNT+ complexes also suppressed the growth of human HeLa cells both in vitro and when injected into tumors in nude mice. Conclusions: -CONH-(CH 2 ) 6 -NH 3 + Cl − functionalized SWNTs carry complexed siRNA into tumor cells, wherein they release the siRNA from the nanotube sidewalls to silence the targeted gene. The -CONH-(CH 2 ) 6 -NH 3 + Cl − functionalized SWNTs may represent a new class of molecular transporters applicable for siRNA therapeutics.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>DOI: 10.1158/1078-0432.CCR-05-2831</identifier><identifier>PMID: 16914582</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Animals ; Antineoplastic agents ; Biological and medical sciences ; Female ; Gene Silencing ; General aspects ; General pharmacology ; HeLa cell ; HeLa Cells ; Humans ; Medical sciences ; Mice ; Nanotubes, Carbon - chemistry ; Neoplasms, Experimental - genetics ; Neoplasms, Experimental - metabolism ; Neoplasms, Experimental - pathology ; Neoplasms, Experimental - therapy ; Pharmaceutical technology. Pharmaceutical industry ; Pharmacology. Drug treatments ; RNA, Small Interfering - administration &amp; dosage ; RNA, Small Interfering - chemistry ; RNA, Small Interfering - genetics ; RNA, Small Interfering - pharmacokinetics ; RNAi ; single-walled carbon nanotubes ; siRNA ; Telomerase - antagonists &amp; inhibitors ; Telomerase - genetics ; telomerase reverse transcriptase ; Transfection</subject><ispartof>Clinical cancer research, 2006-08, Vol.12 (16), p.4933-4939</ispartof><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c501t-14436c65857c124f9577141abd1ca8ed5cb9f5029a233ea31633247a1a059cb33</citedby><cites>FETCH-LOGICAL-c501t-14436c65857c124f9577141abd1ca8ed5cb9f5029a233ea31633247a1a059cb33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,3357,27928,27929</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=18052145$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16914582$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Zhuohan</creatorcontrib><creatorcontrib>Yang, Xiaoying</creatorcontrib><creatorcontrib>Zhang, Yuan</creatorcontrib><creatorcontrib>Zeng, Bin</creatorcontrib><creatorcontrib>Wang, Shujing</creatorcontrib><creatorcontrib>Zhu, Tianhui</creatorcontrib><creatorcontrib>Roden, Richard B S</creatorcontrib><creatorcontrib>Chen, Yongsheng</creatorcontrib><creatorcontrib>Yang, Rongcun</creatorcontrib><title>Delivery of Telomerase Reverse Transcriptase Small Interfering RNA in Complex with Positively Charged Single-Walled Carbon Nanotubes Suppresses Tumor Growth</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>Purpose: To determine whether -CONH-(CH 2 ) 6 -NH 3 + Cl − functionalized single-walled carbon nanotubes (SWNT) carrying complexed small interfering RNA (siRNA) can enter into tumor cells, wherein they release the siRNA to silence the targeted gene. Experimental Design: -CONH-(CH 2 ) 6 -NH 3 + Cl − was used to mediate the conjugation of telomerase reverse transcriptase (TERT) siRNA to SWNTs. The ability of TERT siRNA delivered via SWNT complexes to silence the expression of TERT was assessed by their effects on the proliferation and growth of tumor cells both in vitro and in mouse models. Results: The functionalized SWNTs -CONH-(CH 2 ) 6 -NH 3 + Cl − could facilitate the coupling of siRNAs that specifically target murine TERT expression to form the mTERT siRNA:SWNT+ complex. These functionalized SWNTs rapidly entered three cultured murine tumor cell lines, suppressed mTERT expression, and produced growth arrest. Injection of mTERT siRNA:SWNT+ complexes into s.c. Lewis lung tumors reduced tumor growth. Furthermore, human TERT siRNA:SWNT+ complexes also suppressed the growth of human HeLa cells both in vitro and when injected into tumors in nude mice. Conclusions: -CONH-(CH 2 ) 6 -NH 3 + Cl − functionalized SWNTs carry complexed siRNA into tumor cells, wherein they release the siRNA from the nanotube sidewalls to silence the targeted gene. The -CONH-(CH 2 ) 6 -NH 3 + Cl − functionalized SWNTs may represent a new class of molecular transporters applicable for siRNA therapeutics.</description><subject>Animals</subject><subject>Antineoplastic agents</subject><subject>Biological and medical sciences</subject><subject>Female</subject><subject>Gene Silencing</subject><subject>General aspects</subject><subject>General pharmacology</subject><subject>HeLa cell</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Nanotubes, Carbon - chemistry</subject><subject>Neoplasms, Experimental - genetics</subject><subject>Neoplasms, Experimental - metabolism</subject><subject>Neoplasms, Experimental - pathology</subject><subject>Neoplasms, Experimental - therapy</subject><subject>Pharmaceutical technology. Pharmaceutical industry</subject><subject>Pharmacology. Drug treatments</subject><subject>RNA, Small Interfering - administration &amp; dosage</subject><subject>RNA, Small Interfering - chemistry</subject><subject>RNA, Small Interfering - genetics</subject><subject>RNA, Small Interfering - pharmacokinetics</subject><subject>RNAi</subject><subject>single-walled carbon nanotubes</subject><subject>siRNA</subject><subject>Telomerase - antagonists &amp; inhibitors</subject><subject>Telomerase - genetics</subject><subject>telomerase reverse transcriptase</subject><subject>Transfection</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkd1u1DAQhSMEoqXwCCDfgMRFin_zc1kFKJWqgnYXcWk53snGyInDOGHZd-Fh8WoX9WrGo-_MyOdk2WtGrxlT1QdGyyqnUvDrplnlVOW8EuxJdsmUKnPBC_U09f-Zi-xFjD8pZZJR-Ty7YEXNpKr4Zfb3I3j3G_BAQkc24MMAaCKQFaRhqhs0Y7Topvk4XQ_Ge3I3zoAdoBt3ZPVwQ9xImjBMHv6QvZt78i1EN6el_kCa3uAOtmSdWA_5jyRPr8ZgG0byYMYwLy1Esl6mCSHG1G6WISC5xbCf-5fZs874CK_O9Sr7_vnTpvmS33-9vWtu7nOrKJtzJqUobKEqVVrGZVerskw_Ne2WWVPBVtm27hTlteFCgBGsEILL0jBDVW1bIa6yd6e9E4ZfC8RZDy5a8N6MEJaoWS0LJYoigeoEWgwxInR6QjcYPGhG9TEWfbRcHy3XKRZNlT7GknRvzgeWdoDto-qcQwLengETrfFdct26-MhVVPFEJu79ievdrt87BG0TCZjMA4O214ynpVrWQoh_M_6l7Q</recordid><startdate>20060815</startdate><enddate>20060815</enddate><creator>Zhang, Zhuohan</creator><creator>Yang, Xiaoying</creator><creator>Zhang, Yuan</creator><creator>Zeng, Bin</creator><creator>Wang, Shujing</creator><creator>Zhu, Tianhui</creator><creator>Roden, Richard B S</creator><creator>Chen, Yongsheng</creator><creator>Yang, Rongcun</creator><general>American Association for Cancer Research</general><scope>IQODW</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>7QO</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20060815</creationdate><title>Delivery of Telomerase Reverse Transcriptase Small Interfering RNA in Complex with Positively Charged Single-Walled Carbon Nanotubes Suppresses Tumor Growth</title><author>Zhang, Zhuohan ; Yang, Xiaoying ; Zhang, Yuan ; Zeng, Bin ; Wang, Shujing ; Zhu, Tianhui ; Roden, Richard B S ; Chen, Yongsheng ; Yang, Rongcun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c501t-14436c65857c124f9577141abd1ca8ed5cb9f5029a233ea31633247a1a059cb33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Animals</topic><topic>Antineoplastic agents</topic><topic>Biological and medical sciences</topic><topic>Female</topic><topic>Gene Silencing</topic><topic>General aspects</topic><topic>General pharmacology</topic><topic>HeLa cell</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Nanotubes, Carbon - chemistry</topic><topic>Neoplasms, Experimental - genetics</topic><topic>Neoplasms, Experimental - metabolism</topic><topic>Neoplasms, Experimental - pathology</topic><topic>Neoplasms, Experimental - therapy</topic><topic>Pharmaceutical technology. Pharmaceutical industry</topic><topic>Pharmacology. Drug treatments</topic><topic>RNA, Small Interfering - administration &amp; dosage</topic><topic>RNA, Small Interfering - chemistry</topic><topic>RNA, Small Interfering - genetics</topic><topic>RNA, Small Interfering - pharmacokinetics</topic><topic>RNAi</topic><topic>single-walled carbon nanotubes</topic><topic>siRNA</topic><topic>Telomerase - antagonists &amp; inhibitors</topic><topic>Telomerase - genetics</topic><topic>telomerase reverse transcriptase</topic><topic>Transfection</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Zhuohan</creatorcontrib><creatorcontrib>Yang, Xiaoying</creatorcontrib><creatorcontrib>Zhang, Yuan</creatorcontrib><creatorcontrib>Zeng, Bin</creatorcontrib><creatorcontrib>Wang, Shujing</creatorcontrib><creatorcontrib>Zhu, Tianhui</creatorcontrib><creatorcontrib>Roden, Richard B S</creatorcontrib><creatorcontrib>Chen, Yongsheng</creatorcontrib><creatorcontrib>Yang, Rongcun</creatorcontrib><collection>Pascal-Francis</collection><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>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Zhuohan</au><au>Yang, Xiaoying</au><au>Zhang, Yuan</au><au>Zeng, Bin</au><au>Wang, Shujing</au><au>Zhu, Tianhui</au><au>Roden, Richard B S</au><au>Chen, Yongsheng</au><au>Yang, Rongcun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Delivery of Telomerase Reverse Transcriptase Small Interfering RNA in Complex with Positively Charged Single-Walled Carbon Nanotubes Suppresses Tumor Growth</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2006-08-15</date><risdate>2006</risdate><volume>12</volume><issue>16</issue><spage>4933</spage><epage>4939</epage><pages>4933-4939</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><abstract>Purpose: To determine whether -CONH-(CH 2 ) 6 -NH 3 + Cl − functionalized single-walled carbon nanotubes (SWNT) carrying complexed small interfering RNA (siRNA) can enter into tumor cells, wherein they release the siRNA to silence the targeted gene. Experimental Design: -CONH-(CH 2 ) 6 -NH 3 + Cl − was used to mediate the conjugation of telomerase reverse transcriptase (TERT) siRNA to SWNTs. The ability of TERT siRNA delivered via SWNT complexes to silence the expression of TERT was assessed by their effects on the proliferation and growth of tumor cells both in vitro and in mouse models. Results: The functionalized SWNTs -CONH-(CH 2 ) 6 -NH 3 + Cl − could facilitate the coupling of siRNAs that specifically target murine TERT expression to form the mTERT siRNA:SWNT+ complex. These functionalized SWNTs rapidly entered three cultured murine tumor cell lines, suppressed mTERT expression, and produced growth arrest. Injection of mTERT siRNA:SWNT+ complexes into s.c. Lewis lung tumors reduced tumor growth. Furthermore, human TERT siRNA:SWNT+ complexes also suppressed the growth of human HeLa cells both in vitro and when injected into tumors in nude mice. Conclusions: -CONH-(CH 2 ) 6 -NH 3 + Cl − functionalized SWNTs carry complexed siRNA into tumor cells, wherein they release the siRNA from the nanotube sidewalls to silence the targeted gene. The -CONH-(CH 2 ) 6 -NH 3 + Cl − functionalized SWNTs may represent a new class of molecular transporters applicable for siRNA therapeutics.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>16914582</pmid><doi>10.1158/1078-0432.CCR-05-2831</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record>
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source MEDLINE; American Association for Cancer Research; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection
subjects Animals
Antineoplastic agents
Biological and medical sciences
Female
Gene Silencing
General aspects
General pharmacology
HeLa cell
HeLa Cells
Humans
Medical sciences
Mice
Nanotubes, Carbon - chemistry
Neoplasms, Experimental - genetics
Neoplasms, Experimental - metabolism
Neoplasms, Experimental - pathology
Neoplasms, Experimental - therapy
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
RNA, Small Interfering - administration & dosage
RNA, Small Interfering - chemistry
RNA, Small Interfering - genetics
RNA, Small Interfering - pharmacokinetics
RNAi
single-walled carbon nanotubes
siRNA
Telomerase - antagonists & inhibitors
Telomerase - genetics
telomerase reverse transcriptase
Transfection
title Delivery of Telomerase Reverse Transcriptase Small Interfering RNA in Complex with Positively Charged Single-Walled Carbon Nanotubes Suppresses Tumor Growth
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