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...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Journal of the American Chemical Society 2014-02, Vol.136 (7), p.2731-2734
Hauptverfasser: Wang, RuoWen, Zhu, Guizhi, Mei, Lei, Xie, Yan, Ma, Haibin, Ye, Mao, Qing, Feng-Ling, Tan, Weihong
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 2734
container_issue 7
container_start_page 2731
container_title Journal of the American Chemical Society
container_volume 136
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
format Article
fullrecord <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3985443</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2000323566</sourcerecordid><originalsourceid>FETCH-LOGICAL-a504t-76f6173f6211904d35293d67424e70c7ddb2bb4f28c9d0dfe15a48144409b5193</originalsourceid><addsrcrecordid>eNqFkc1Kw0AUhQdRbK0ufAHJRtBFdP4z2Qil9Q8UF9X1MMlM2pQkU2eSQne-g2_okzhaLQqCq8vlfvdw7zkAHCJ4hiBG53NFEUpIyrZAHzEMY4Yw3wZ9CCGOE8FJD-x5Pw8txQLtgh6mVBCOkz6YDLvW1qo1Orq3uquUiyarpp0ZX_rIFtFw0arauLeX17HrptHINvNuGnAfFdZFj8pNzcfu53BsqnJp3Gof7BSq8ubgqw7A09Xl4-gmvnu4vh0N72LFIG3jhBc8XF1wjFAKqSYMp0TzhGJqEpgnWmc4y2iBRZ5qqAuDmKICUUphmjGUkgG4WOsuuqw2OjdN61QlF66slVtJq0r5e9KUMzm1S0lSwSglQeDkS8DZ5874Vtalz01VqcbYzkscHCOYMM7_RRGDkAuBBAvo6RrNnfXemWJzEYLyIy-5ySuwRz9f2JDfAQXgeA2o3Mu57VwTHP1D6B1U8Zw2</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1500688185</pqid></control><display><type>article</type><title>Automated Modular Synthesis of Aptamer–Drug Conjugates for Targeted Drug Delivery</title><source>ACS Publications</source><source>MEDLINE</source><creator>Wang, RuoWen ; Zhu, Guizhi ; Mei, Lei ; Xie, Yan ; Ma, Haibin ; Ye, Mao ; Qing, Feng-Ling ; Tan, Weihong</creator><creatorcontrib>Wang, RuoWen ; Zhu, Guizhi ; Mei, Lei ; Xie, Yan ; Ma, Haibin ; Ye, Mao ; Qing, Feng-Ling ; Tan, Weihong</creatorcontrib><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><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>
fulltext fulltext
identifier ISSN: 0002-7863
ispartof Journal of the American Chemical Society, 2014-02, Vol.136 (7), p.2731-2734
issn 0002-7863
1520-5126
1520-5126
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3985443
source ACS Publications; MEDLINE
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
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-02T08%3A04%3A07IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Automated%20Modular%20Synthesis%20of%20Aptamer%E2%80%93Drug%20Conjugates%20for%20Targeted%20Drug%20Delivery&rft.jtitle=Journal%20of%20the%20American%20Chemical%20Society&rft.au=Wang,%20RuoWen&rft.date=2014-02-19&rft.volume=136&rft.issue=7&rft.spage=2731&rft.epage=2734&rft.pages=2731-2734&rft.issn=0002-7863&rft.eissn=1520-5126&rft_id=info:doi/10.1021/ja4117395&rft_dat=%3Cproquest_pubme%3E2000323566%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1500688185&rft_id=info:pmid/24483627&rfr_iscdi=true