A Novel Fluorescent Gemcitabine Prodrug That Follows a Nucleoside Transporter‐Independent Internalization and Bears Enhanced Therapeutic Efficacy With Respect to Gemcitabine
The multiplexity of cancer has rendered it the second leading cause of mortality worldwide and theragnostic prodrugs have gained popularity in recent years as a means of treatment. Theragnostic prodrugs enable the simultaneous diagnosis and therapy of tumors via high‐precision real‐time drug release...
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| creator | Vrettos, Eirinaios Ι. Kyrkou, Stavroula G. Zoi, Vasiliki Giannakopoulou, Maria Chatziathanasiadou, Maria V. Kanaki, Zoi Agalou, Adamantia Bistas, Vasileios‐Panagiotis Kougioumtzi, Anastasia Karampelas, Theodoros Diamantis, Dimitrios A. Murphy, Carol Beis, Dimitris Klinakis, Apostolos Tamvakopoulos, Constantin Kyritsis, Athanasios P. Alexiou, George A. Tzakos, Andreas G. |
| description | The multiplexity of cancer has rendered it the second leading cause of mortality worldwide and theragnostic prodrugs have gained popularity in recent years as a means of treatment. Theragnostic prodrugs enable the simultaneous diagnosis and therapy of tumors via high‐precision real‐time drug release monitoring. Herein, we report the development of the small theragnostic prodrug GF, based on the nucleoside anticancer agent gemcitabine and the fluorescent dye 5(6)‐carboxyfluorescein. We have successfully demonstrated its efficient internalization in tumor cells, showing localization throughout both the early and late endocytic pathways. Its mechanism of cell internalization was evaluated, confirming its independence from nucleoside transporters. Its cellular localization via confocal microscopy revealed a clathrin‐mediated endocytosis mechanism, distinguishing it from analogous compounds studied previously. Furthermore, GF exhibited stability across various pH values and in human blood plasma. Subsequently, its in vitro cytotoxicity was assessed in three human cancer cell lines (A549, U87 and T98). Additionally, its pharmacokinetic profile in mice was investigated and the consequent drug release was monitored. Finally, its in vivo visualization was accomplished in zebrafish xenotransplantation models and its in vivo efficacy was evaluated in A549 xenografts. The results unveiled an intriguing efficacy profile, positioning GF as a compelling candidate warranting further investigation.
A fluorescent prodrug, named GF, based on gemcitabine and 5(6)‐carboxyfluorescein was developed in a single step. GF follows a nucleoside transporter‐independent endocytosis internalization mechanism, surpassing a key resistance mechanism against gemcitabine. Its pharmacokinetic profile and drug release efficiency were evaluated in mice, and eventually its visualization was achieved in zebrafish and its tumor inhibition was monitored in A549 xenografted mice. |
| doi_str_mv | 10.1002/chem.202401327 |
| format | Article |
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A fluorescent prodrug, named GF, based on gemcitabine and 5(6)‐carboxyfluorescein was developed in a single step. GF follows a nucleoside transporter‐independent endocytosis internalization mechanism, surpassing a key resistance mechanism against gemcitabine. Its pharmacokinetic profile and drug release efficiency were evaluated in mice, and eventually its visualization was achieved in zebrafish and its tumor inhibition was monitored in A549 xenografted mice.</description><identifier>ISSN: 0947-6539</identifier><identifier>ISSN: 1521-3765</identifier><identifier>EISSN: 1521-3765</identifier><identifier>DOI: 10.1002/chem.202401327</identifier><identifier>PMID: 38941241</identifier><language>eng</language><publisher>Germany: Wiley Subscription Services, Inc</publisher><subject>Animal models ; Animals ; Antineoplastic Agents - chemistry ; Antineoplastic Agents - pharmacology ; Antineoplastic drugs ; Biocompatibility ; Blood plasma ; Cell Line, Tumor ; Clathrin ; Confocal microscopy ; Cytotoxicity ; Deoxycytidine - analogs & derivatives ; Deoxycytidine - chemistry ; Deoxycytidine - pharmacology ; Drug Liberation ; Drugs ; Effectiveness ; Endocytosis ; Endocytosis - drug effects ; Fluoresceins - chemistry ; Fluorescence ; Fluorescent dyes ; Fluorescent Dyes - chemistry ; Fluorescent indicators ; Gemcitabine ; Humans ; In vivo methods and tests ; Internalization ; Localization ; Mice ; Nucleoside analogs ; Nucleoside Transport Proteins - metabolism ; Nucleoside transporter ; Nucleosides ; Pharmacokinetics ; Prodrug ; Prodrugs ; Prodrugs - chemistry ; Prodrugs - pharmacology ; Theragnostic ; Tumor cell lines ; Tumor cells ; Tumors ; Xenografts ; Xenotransplantation ; Zebrafish</subject><ispartof>Chemistry : a European journal, 2024-09, Vol.30 (50), p.e202401327-n/a</ispartof><rights>2024 The Authors. 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Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c2987-a22bcf08333df1793f24f64a5a1d13d5fec6dbed13ef851217a259f64331937e3</cites><orcidid>0000-0003-4096-9046 ; 0000-0001-6391-0288 ; 0000-0002-4801-1900</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fchem.202401327$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fchem.202401327$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>315,781,785,1418,27929,27930,45579,45580</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38941241$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Vrettos, Eirinaios Ι.</creatorcontrib><creatorcontrib>Kyrkou, Stavroula G.</creatorcontrib><creatorcontrib>Zoi, Vasiliki</creatorcontrib><creatorcontrib>Giannakopoulou, Maria</creatorcontrib><creatorcontrib>Chatziathanasiadou, Maria V.</creatorcontrib><creatorcontrib>Kanaki, Zoi</creatorcontrib><creatorcontrib>Agalou, Adamantia</creatorcontrib><creatorcontrib>Bistas, Vasileios‐Panagiotis</creatorcontrib><creatorcontrib>Kougioumtzi, Anastasia</creatorcontrib><creatorcontrib>Karampelas, Theodoros</creatorcontrib><creatorcontrib>Diamantis, Dimitrios A.</creatorcontrib><creatorcontrib>Murphy, Carol</creatorcontrib><creatorcontrib>Beis, Dimitris</creatorcontrib><creatorcontrib>Klinakis, Apostolos</creatorcontrib><creatorcontrib>Tamvakopoulos, Constantin</creatorcontrib><creatorcontrib>Kyritsis, Athanasios P.</creatorcontrib><creatorcontrib>Alexiou, George A.</creatorcontrib><creatorcontrib>Tzakos, Andreas G.</creatorcontrib><title>A Novel Fluorescent Gemcitabine Prodrug That Follows a Nucleoside Transporter‐Independent Internalization and Bears Enhanced Therapeutic Efficacy With Respect to Gemcitabine</title><title>Chemistry : a European journal</title><addtitle>Chemistry</addtitle><description>The multiplexity of cancer has rendered it the second leading cause of mortality worldwide and theragnostic prodrugs have gained popularity in recent years as a means of treatment. Theragnostic prodrugs enable the simultaneous diagnosis and therapy of tumors via high‐precision real‐time drug release monitoring. Herein, we report the development of the small theragnostic prodrug GF, based on the nucleoside anticancer agent gemcitabine and the fluorescent dye 5(6)‐carboxyfluorescein. We have successfully demonstrated its efficient internalization in tumor cells, showing localization throughout both the early and late endocytic pathways. Its mechanism of cell internalization was evaluated, confirming its independence from nucleoside transporters. Its cellular localization via confocal microscopy revealed a clathrin‐mediated endocytosis mechanism, distinguishing it from analogous compounds studied previously. Furthermore, GF exhibited stability across various pH values and in human blood plasma. Subsequently, its in vitro cytotoxicity was assessed in three human cancer cell lines (A549, U87 and T98). Additionally, its pharmacokinetic profile in mice was investigated and the consequent drug release was monitored. Finally, its in vivo visualization was accomplished in zebrafish xenotransplantation models and its in vivo efficacy was evaluated in A549 xenografts. The results unveiled an intriguing efficacy profile, positioning GF as a compelling candidate warranting further investigation.
A fluorescent prodrug, named GF, based on gemcitabine and 5(6)‐carboxyfluorescein was developed in a single step. GF follows a nucleoside transporter‐independent endocytosis internalization mechanism, surpassing a key resistance mechanism against gemcitabine. Its pharmacokinetic profile and drug release efficiency were evaluated in mice, and eventually its visualization was achieved in zebrafish and its tumor inhibition was monitored in A549 xenografted mice.</description><subject>Animal models</subject><subject>Animals</subject><subject>Antineoplastic Agents - chemistry</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antineoplastic drugs</subject><subject>Biocompatibility</subject><subject>Blood plasma</subject><subject>Cell Line, Tumor</subject><subject>Clathrin</subject><subject>Confocal microscopy</subject><subject>Cytotoxicity</subject><subject>Deoxycytidine - analogs & derivatives</subject><subject>Deoxycytidine - chemistry</subject><subject>Deoxycytidine - pharmacology</subject><subject>Drug Liberation</subject><subject>Drugs</subject><subject>Effectiveness</subject><subject>Endocytosis</subject><subject>Endocytosis - drug effects</subject><subject>Fluoresceins - chemistry</subject><subject>Fluorescence</subject><subject>Fluorescent dyes</subject><subject>Fluorescent Dyes - chemistry</subject><subject>Fluorescent indicators</subject><subject>Gemcitabine</subject><subject>Humans</subject><subject>In vivo methods and tests</subject><subject>Internalization</subject><subject>Localization</subject><subject>Mice</subject><subject>Nucleoside analogs</subject><subject>Nucleoside Transport Proteins - metabolism</subject><subject>Nucleoside transporter</subject><subject>Nucleosides</subject><subject>Pharmacokinetics</subject><subject>Prodrug</subject><subject>Prodrugs</subject><subject>Prodrugs - chemistry</subject><subject>Prodrugs - pharmacology</subject><subject>Theragnostic</subject><subject>Tumor cell lines</subject><subject>Tumor cells</subject><subject>Tumors</subject><subject>Xenografts</subject><subject>Xenotransplantation</subject><subject>Zebrafish</subject><issn>0947-6539</issn><issn>1521-3765</issn><issn>1521-3765</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>EIF</sourceid><recordid>eNqFkctuEzEUhi1ERUNhyxJZYtPNpL7MJbMsUdJGagtCQSxHjn1MXHnswfZQhRWPwJvwTjwJjtIWxIaNj2V959Px-RF6RcmUEsLO5Bb6KSOsJJSz5gma0IrRgjd19RRNSFs2RV3x9hg9j_GWENLWnD9Dx3zWlpSVdIJ-nuMb_xUsXtrRB4gSXMIX0EuTxMY4wO-DV2H8jNdbkfDSW-vvIhb4ZpQWfDQK8DoIFwcfEoRf33-snIIB8pE9K5ffnLDmm0jGOyycwm9BhIgXbiucBJW1EMQAYzISL7Q2Usgd_mTSFn-AOIBMOPm_53mBjrSwEV7e1xP0cblYzy-Lq3cXq_n5VSFZO2sKwdhGajLjnCtNm5ZrVuq6FJWginJVaZC12kC-g55VlNFGsKrNBOe05Q3wE3R68A7Bfxkhpq43eTnWCgd-jB0nDa-rklVlRt_8g976cf_tTNG8cdqQmmZqeqBk8DEG0N0QTC_CrqOk20fZ7aPsHqPMDa_vteOmB_WIP2SXgfYA3BkLu__ouvnl4vqP_Ddkba5s</recordid><startdate>20240905</startdate><enddate>20240905</enddate><creator>Vrettos, Eirinaios Ι.</creator><creator>Kyrkou, Stavroula G.</creator><creator>Zoi, Vasiliki</creator><creator>Giannakopoulou, Maria</creator><creator>Chatziathanasiadou, Maria V.</creator><creator>Kanaki, Zoi</creator><creator>Agalou, Adamantia</creator><creator>Bistas, Vasileios‐Panagiotis</creator><creator>Kougioumtzi, Anastasia</creator><creator>Karampelas, Theodoros</creator><creator>Diamantis, Dimitrios A.</creator><creator>Murphy, Carol</creator><creator>Beis, Dimitris</creator><creator>Klinakis, Apostolos</creator><creator>Tamvakopoulos, Constantin</creator><creator>Kyritsis, Athanasios P.</creator><creator>Alexiou, George A.</creator><creator>Tzakos, Andreas G.</creator><general>Wiley Subscription Services, Inc</general><scope>24P</scope><scope>WIN</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>7SR</scope><scope>8BQ</scope><scope>8FD</scope><scope>JG9</scope><scope>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-4096-9046</orcidid><orcidid>https://orcid.org/0000-0001-6391-0288</orcidid><orcidid>https://orcid.org/0000-0002-4801-1900</orcidid></search><sort><creationdate>20240905</creationdate><title>A Novel Fluorescent Gemcitabine Prodrug That Follows a Nucleoside Transporter‐Independent Internalization and Bears Enhanced Therapeutic Efficacy With Respect to Gemcitabine</title><author>Vrettos, Eirinaios Ι. ; Kyrkou, Stavroula G. ; Zoi, Vasiliki ; Giannakopoulou, Maria ; Chatziathanasiadou, Maria V. ; Kanaki, Zoi ; Agalou, Adamantia ; Bistas, Vasileios‐Panagiotis ; Kougioumtzi, Anastasia ; Karampelas, Theodoros ; Diamantis, Dimitrios A. ; Murphy, Carol ; Beis, Dimitris ; Klinakis, Apostolos ; Tamvakopoulos, Constantin ; Kyritsis, Athanasios P. ; Alexiou, George A. ; Tzakos, Andreas G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2987-a22bcf08333df1793f24f64a5a1d13d5fec6dbed13ef851217a259f64331937e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Animal models</topic><topic>Animals</topic><topic>Antineoplastic Agents - chemistry</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Antineoplastic drugs</topic><topic>Biocompatibility</topic><topic>Blood plasma</topic><topic>Cell Line, Tumor</topic><topic>Clathrin</topic><topic>Confocal microscopy</topic><topic>Cytotoxicity</topic><topic>Deoxycytidine - analogs & derivatives</topic><topic>Deoxycytidine - chemistry</topic><topic>Deoxycytidine - pharmacology</topic><topic>Drug Liberation</topic><topic>Drugs</topic><topic>Effectiveness</topic><topic>Endocytosis</topic><topic>Endocytosis - drug effects</topic><topic>Fluoresceins - chemistry</topic><topic>Fluorescence</topic><topic>Fluorescent dyes</topic><topic>Fluorescent Dyes - chemistry</topic><topic>Fluorescent indicators</topic><topic>Gemcitabine</topic><topic>Humans</topic><topic>In vivo methods and tests</topic><topic>Internalization</topic><topic>Localization</topic><topic>Mice</topic><topic>Nucleoside analogs</topic><topic>Nucleoside Transport Proteins - metabolism</topic><topic>Nucleoside transporter</topic><topic>Nucleosides</topic><topic>Pharmacokinetics</topic><topic>Prodrug</topic><topic>Prodrugs</topic><topic>Prodrugs - chemistry</topic><topic>Prodrugs - pharmacology</topic><topic>Theragnostic</topic><topic>Tumor cell lines</topic><topic>Tumor cells</topic><topic>Tumors</topic><topic>Xenografts</topic><topic>Xenotransplantation</topic><topic>Zebrafish</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Vrettos, Eirinaios Ι.</creatorcontrib><creatorcontrib>Kyrkou, Stavroula G.</creatorcontrib><creatorcontrib>Zoi, Vasiliki</creatorcontrib><creatorcontrib>Giannakopoulou, Maria</creatorcontrib><creatorcontrib>Chatziathanasiadou, Maria V.</creatorcontrib><creatorcontrib>Kanaki, Zoi</creatorcontrib><creatorcontrib>Agalou, Adamantia</creatorcontrib><creatorcontrib>Bistas, Vasileios‐Panagiotis</creatorcontrib><creatorcontrib>Kougioumtzi, Anastasia</creatorcontrib><creatorcontrib>Karampelas, Theodoros</creatorcontrib><creatorcontrib>Diamantis, Dimitrios A.</creatorcontrib><creatorcontrib>Murphy, Carol</creatorcontrib><creatorcontrib>Beis, Dimitris</creatorcontrib><creatorcontrib>Klinakis, Apostolos</creatorcontrib><creatorcontrib>Tamvakopoulos, Constantin</creatorcontrib><creatorcontrib>Kyritsis, Athanasios P.</creatorcontrib><creatorcontrib>Alexiou, George A.</creatorcontrib><creatorcontrib>Tzakos, Andreas G.</creatorcontrib><collection>Wiley-Blackwell Open Access Titles</collection><collection>Wiley Free Content</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Engineered Materials Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Materials Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Chemistry : a European journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Vrettos, Eirinaios Ι.</au><au>Kyrkou, Stavroula G.</au><au>Zoi, Vasiliki</au><au>Giannakopoulou, Maria</au><au>Chatziathanasiadou, Maria V.</au><au>Kanaki, Zoi</au><au>Agalou, Adamantia</au><au>Bistas, Vasileios‐Panagiotis</au><au>Kougioumtzi, Anastasia</au><au>Karampelas, Theodoros</au><au>Diamantis, Dimitrios A.</au><au>Murphy, Carol</au><au>Beis, Dimitris</au><au>Klinakis, Apostolos</au><au>Tamvakopoulos, Constantin</au><au>Kyritsis, Athanasios P.</au><au>Alexiou, George A.</au><au>Tzakos, Andreas G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Novel Fluorescent Gemcitabine Prodrug That Follows a Nucleoside Transporter‐Independent Internalization and Bears Enhanced Therapeutic Efficacy With Respect to Gemcitabine</atitle><jtitle>Chemistry : a European journal</jtitle><addtitle>Chemistry</addtitle><date>2024-09-05</date><risdate>2024</risdate><volume>30</volume><issue>50</issue><spage>e202401327</spage><epage>n/a</epage><pages>e202401327-n/a</pages><issn>0947-6539</issn><issn>1521-3765</issn><eissn>1521-3765</eissn><abstract>The multiplexity of cancer has rendered it the second leading cause of mortality worldwide and theragnostic prodrugs have gained popularity in recent years as a means of treatment. Theragnostic prodrugs enable the simultaneous diagnosis and therapy of tumors via high‐precision real‐time drug release monitoring. Herein, we report the development of the small theragnostic prodrug GF, based on the nucleoside anticancer agent gemcitabine and the fluorescent dye 5(6)‐carboxyfluorescein. We have successfully demonstrated its efficient internalization in tumor cells, showing localization throughout both the early and late endocytic pathways. Its mechanism of cell internalization was evaluated, confirming its independence from nucleoside transporters. Its cellular localization via confocal microscopy revealed a clathrin‐mediated endocytosis mechanism, distinguishing it from analogous compounds studied previously. Furthermore, GF exhibited stability across various pH values and in human blood plasma. Subsequently, its in vitro cytotoxicity was assessed in three human cancer cell lines (A549, U87 and T98). Additionally, its pharmacokinetic profile in mice was investigated and the consequent drug release was monitored. Finally, its in vivo visualization was accomplished in zebrafish xenotransplantation models and its in vivo efficacy was evaluated in A549 xenografts. The results unveiled an intriguing efficacy profile, positioning GF as a compelling candidate warranting further investigation.
A fluorescent prodrug, named GF, based on gemcitabine and 5(6)‐carboxyfluorescein was developed in a single step. GF follows a nucleoside transporter‐independent endocytosis internalization mechanism, surpassing a key resistance mechanism against gemcitabine. Its pharmacokinetic profile and drug release efficiency were evaluated in mice, and eventually its visualization was achieved in zebrafish and its tumor inhibition was monitored in A549 xenografted mice.</abstract><cop>Germany</cop><pub>Wiley Subscription Services, Inc</pub><pmid>38941241</pmid><doi>10.1002/chem.202401327</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0003-4096-9046</orcidid><orcidid>https://orcid.org/0000-0001-6391-0288</orcidid><orcidid>https://orcid.org/0000-0002-4801-1900</orcidid><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0947-6539 |
| ispartof | Chemistry : a European journal, 2024-09, Vol.30 (50), p.e202401327-n/a |
| issn | 0947-6539 1521-3765 1521-3765 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_3073654254 |
| source | MEDLINE; Wiley Online Library All Journals |
| subjects | Animal models Animals Antineoplastic Agents - chemistry Antineoplastic Agents - pharmacology Antineoplastic drugs Biocompatibility Blood plasma Cell Line, Tumor Clathrin Confocal microscopy Cytotoxicity Deoxycytidine - analogs & derivatives Deoxycytidine - chemistry Deoxycytidine - pharmacology Drug Liberation Drugs Effectiveness Endocytosis Endocytosis - drug effects Fluoresceins - chemistry Fluorescence Fluorescent dyes Fluorescent Dyes - chemistry Fluorescent indicators Gemcitabine Humans In vivo methods and tests Internalization Localization Mice Nucleoside analogs Nucleoside Transport Proteins - metabolism Nucleoside transporter Nucleosides Pharmacokinetics Prodrug Prodrugs Prodrugs - chemistry Prodrugs - pharmacology Theragnostic Tumor cell lines Tumor cells Tumors Xenografts Xenotransplantation Zebrafish |
| title | A Novel Fluorescent Gemcitabine Prodrug That Follows a Nucleoside Transporter‐Independent Internalization and Bears Enhanced Therapeutic Efficacy With Respect to Gemcitabine |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-15T05%3A19%3A52IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20Novel%20Fluorescent%20Gemcitabine%20Prodrug%20That%20Follows%20a%20Nucleoside%20Transporter%E2%80%90Independent%20Internalization%20and%20Bears%20Enhanced%20Therapeutic%20Efficacy%20With%20Respect%20to%20Gemcitabine&rft.jtitle=Chemistry%20:%20a%20European%20journal&rft.au=Vrettos,%20Eirinaios%20%CE%99.&rft.date=2024-09-05&rft.volume=30&rft.issue=50&rft.spage=e202401327&rft.epage=n/a&rft.pages=e202401327-n/a&rft.issn=0947-6539&rft.eissn=1521-3765&rft_id=info:doi/10.1002/chem.202401327&rft_dat=%3Cproquest_cross%3E3073654254%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=3109617061&rft_id=info:pmid/38941241&rfr_iscdi=true |