Automated Modular Synthesis of Aptamer–Drug Conjugates for Targeted Drug Delivery
Aptamer–drug conjugates (ApDCs) are promising targeted drug delivery systems for reducing toxicity while increasing the efficacy of chemotherapy. However, current ApDC technologies suffer from problems caused by the complicated preparation and low controllability of drug–aptamer conjugation. To solv...
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Veröffentlicht in: | Journal of the American Chemical Society 2014-02, Vol.136 (7), p.2731-2734 |
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creator | Wang, RuoWen Zhu, Guizhi Mei, Lei Xie, Yan Ma, Haibin Ye, Mao Qing, Feng-Ling Tan, Weihong |
description | Aptamer–drug conjugates (ApDCs) are promising targeted drug delivery systems for reducing toxicity while increasing the efficacy of chemotherapy. However, current ApDC technologies suffer from problems caused by the complicated preparation and low controllability of drug–aptamer conjugation. To solve such problems, we have designed and synthesized a therapeutic module for solid phase synthesis, which is a phosphoramdite containing an anticancer drug moiety and a photocleavable linker. Using this module, we have realized automated and modular synthesis of ApDCs, and multiple drugs were efficiently incorporated into ApDCs at predesigned positions. The ApDCs not only recognize target cancer cells specifically, but also release drugs in a photocontrollable manner. We demonstrated the potential of automated and modular ApDC technology for applications in targeted cancer therapy. |
doi_str_mv | 10.1021/ja4117395 |
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However, current ApDC technologies suffer from problems caused by the complicated preparation and low controllability of drug–aptamer conjugation. To solve such problems, we have designed and synthesized a therapeutic module for solid phase synthesis, which is a phosphoramdite containing an anticancer drug moiety and a photocleavable linker. Using this module, we have realized automated and modular synthesis of ApDCs, and multiple drugs were efficiently incorporated into ApDCs at predesigned positions. The ApDCs not only recognize target cancer cells specifically, but also release drugs in a photocontrollable manner. We demonstrated the potential of automated and modular ApDC technology for applications in targeted cancer therapy.</description><identifier>ISSN: 0002-7863</identifier><identifier>ISSN: 1520-5126</identifier><identifier>EISSN: 1520-5126</identifier><identifier>DOI: 10.1021/ja4117395</identifier><identifier>PMID: 24483627</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Amides - chemistry ; antineoplastic agents ; Antineoplastic Agents - chemistry ; Antineoplastic Agents - metabolism ; Aptamers, Nucleotide - chemistry ; Automation ; Communication ; Drug Carriers - chemical synthesis ; Drug Carriers - chemistry ; drug delivery systems ; drug therapy ; HCT116 Cells ; Humans ; neoplasm cells ; neoplasms ; Phosphoric Acids - chemistry ; Photochemical Processes ; Solid-Phase Synthesis Techniques ; toxicity</subject><ispartof>Journal of the American Chemical Society, 2014-02, Vol.136 (7), p.2731-2734</ispartof><rights>Copyright © 2014 American Chemical Society</rights><rights>Copyright © 2014 American Chemical Society 2014 American Chemical Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a504t-76f6173f6211904d35293d67424e70c7ddb2bb4f28c9d0dfe15a48144409b5193</citedby><cites>FETCH-LOGICAL-a504t-76f6173f6211904d35293d67424e70c7ddb2bb4f28c9d0dfe15a48144409b5193</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/ja4117395$$EPDF$$P50$$Gacs$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/ja4117395$$EHTML$$P50$$Gacs$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,2752,27053,27901,27902,56713,56763</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24483627$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, RuoWen</creatorcontrib><creatorcontrib>Zhu, Guizhi</creatorcontrib><creatorcontrib>Mei, Lei</creatorcontrib><creatorcontrib>Xie, Yan</creatorcontrib><creatorcontrib>Ma, Haibin</creatorcontrib><creatorcontrib>Ye, Mao</creatorcontrib><creatorcontrib>Qing, Feng-Ling</creatorcontrib><creatorcontrib>Tan, Weihong</creatorcontrib><title>Automated Modular Synthesis of Aptamer–Drug Conjugates for Targeted Drug Delivery</title><title>Journal of the American Chemical Society</title><addtitle>J. Am. Chem. Soc</addtitle><description>Aptamer–drug conjugates (ApDCs) are promising targeted drug delivery systems for reducing toxicity while increasing the efficacy of chemotherapy. However, current ApDC technologies suffer from problems caused by the complicated preparation and low controllability of drug–aptamer conjugation. To solve such problems, we have designed and synthesized a therapeutic module for solid phase synthesis, which is a phosphoramdite containing an anticancer drug moiety and a photocleavable linker. Using this module, we have realized automated and modular synthesis of ApDCs, and multiple drugs were efficiently incorporated into ApDCs at predesigned positions. The ApDCs not only recognize target cancer cells specifically, but also release drugs in a photocontrollable manner. We demonstrated the potential of automated and modular ApDC technology for applications in targeted cancer therapy.</description><subject>Amides - chemistry</subject><subject>antineoplastic agents</subject><subject>Antineoplastic Agents - chemistry</subject><subject>Antineoplastic Agents - metabolism</subject><subject>Aptamers, Nucleotide - chemistry</subject><subject>Automation</subject><subject>Communication</subject><subject>Drug Carriers - chemical synthesis</subject><subject>Drug Carriers - chemistry</subject><subject>drug delivery systems</subject><subject>drug therapy</subject><subject>HCT116 Cells</subject><subject>Humans</subject><subject>neoplasm cells</subject><subject>neoplasms</subject><subject>Phosphoric Acids - chemistry</subject><subject>Photochemical Processes</subject><subject>Solid-Phase Synthesis Techniques</subject><subject>toxicity</subject><issn>0002-7863</issn><issn>1520-5126</issn><issn>1520-5126</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>N~.</sourceid><sourceid>EIF</sourceid><recordid>eNqFkc1Kw0AUhQdRbK0ufAHJRtBFdP4z2Qil9Q8UF9X1MMlM2pQkU2eSQne-g2_okzhaLQqCq8vlfvdw7zkAHCJ4hiBG53NFEUpIyrZAHzEMY4Yw3wZ9CCGOE8FJD-x5Pw8txQLtgh6mVBCOkz6YDLvW1qo1Orq3uquUiyarpp0ZX_rIFtFw0arauLeX17HrptHINvNuGnAfFdZFj8pNzcfu53BsqnJp3Gof7BSq8ubgqw7A09Xl4-gmvnu4vh0N72LFIG3jhBc8XF1wjFAKqSYMp0TzhGJqEpgnWmc4y2iBRZ5qqAuDmKICUUphmjGUkgG4WOsuuqw2OjdN61QlF66slVtJq0r5e9KUMzm1S0lSwSglQeDkS8DZ5874Vtalz01VqcbYzkscHCOYMM7_RRGDkAuBBAvo6RrNnfXemWJzEYLyIy-5ySuwRz9f2JDfAQXgeA2o3Mu57VwTHP1D6B1U8Zw2</recordid><startdate>20140219</startdate><enddate>20140219</enddate><creator>Wang, RuoWen</creator><creator>Zhu, Guizhi</creator><creator>Mei, Lei</creator><creator>Xie, Yan</creator><creator>Ma, Haibin</creator><creator>Ye, Mao</creator><creator>Qing, Feng-Ling</creator><creator>Tan, Weihong</creator><general>American Chemical Society</general><scope>N~.</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>7X8</scope><scope>7S9</scope><scope>L.6</scope><scope>5PM</scope></search><sort><creationdate>20140219</creationdate><title>Automated Modular Synthesis of Aptamer–Drug Conjugates for Targeted Drug Delivery</title><author>Wang, RuoWen ; Zhu, Guizhi ; Mei, Lei ; Xie, Yan ; Ma, Haibin ; Ye, Mao ; Qing, Feng-Ling ; Tan, Weihong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a504t-76f6173f6211904d35293d67424e70c7ddb2bb4f28c9d0dfe15a48144409b5193</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Amides - chemistry</topic><topic>antineoplastic agents</topic><topic>Antineoplastic Agents - chemistry</topic><topic>Antineoplastic Agents - metabolism</topic><topic>Aptamers, Nucleotide - chemistry</topic><topic>Automation</topic><topic>Communication</topic><topic>Drug Carriers - chemical synthesis</topic><topic>Drug Carriers - chemistry</topic><topic>drug delivery systems</topic><topic>drug therapy</topic><topic>HCT116 Cells</topic><topic>Humans</topic><topic>neoplasm cells</topic><topic>neoplasms</topic><topic>Phosphoric Acids - chemistry</topic><topic>Photochemical Processes</topic><topic>Solid-Phase Synthesis Techniques</topic><topic>toxicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, RuoWen</creatorcontrib><creatorcontrib>Zhu, Guizhi</creatorcontrib><creatorcontrib>Mei, Lei</creatorcontrib><creatorcontrib>Xie, Yan</creatorcontrib><creatorcontrib>Ma, Haibin</creatorcontrib><creatorcontrib>Ye, Mao</creatorcontrib><creatorcontrib>Qing, Feng-Ling</creatorcontrib><creatorcontrib>Tan, Weihong</creatorcontrib><collection>American Chemical Society (ACS) Open Access</collection><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>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of the American Chemical Society</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, RuoWen</au><au>Zhu, Guizhi</au><au>Mei, Lei</au><au>Xie, Yan</au><au>Ma, Haibin</au><au>Ye, Mao</au><au>Qing, Feng-Ling</au><au>Tan, Weihong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Automated Modular Synthesis of Aptamer–Drug Conjugates for Targeted Drug Delivery</atitle><jtitle>Journal of the American Chemical Society</jtitle><addtitle>J. Am. Chem. Soc</addtitle><date>2014-02-19</date><risdate>2014</risdate><volume>136</volume><issue>7</issue><spage>2731</spage><epage>2734</epage><pages>2731-2734</pages><issn>0002-7863</issn><issn>1520-5126</issn><eissn>1520-5126</eissn><abstract>Aptamer–drug conjugates (ApDCs) are promising targeted drug delivery systems for reducing toxicity while increasing the efficacy of chemotherapy. However, current ApDC technologies suffer from problems caused by the complicated preparation and low controllability of drug–aptamer conjugation. To solve such problems, we have designed and synthesized a therapeutic module for solid phase synthesis, which is a phosphoramdite containing an anticancer drug moiety and a photocleavable linker. Using this module, we have realized automated and modular synthesis of ApDCs, and multiple drugs were efficiently incorporated into ApDCs at predesigned positions. The ApDCs not only recognize target cancer cells specifically, but also release drugs in a photocontrollable manner. We demonstrated the potential of automated and modular ApDC technology for applications in targeted cancer therapy.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>24483627</pmid><doi>10.1021/ja4117395</doi><tpages>4</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Amides - chemistry antineoplastic agents Antineoplastic Agents - chemistry Antineoplastic Agents - metabolism Aptamers, Nucleotide - chemistry Automation Communication Drug Carriers - chemical synthesis Drug Carriers - chemistry drug delivery systems drug therapy HCT116 Cells Humans neoplasm cells neoplasms Phosphoric Acids - chemistry Photochemical Processes Solid-Phase Synthesis Techniques toxicity |
title | Automated Modular Synthesis of Aptamer–Drug Conjugates for Targeted Drug Delivery |
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