A Multi-action and Multi-target Ru II -Pt IV Conjugate Combining Cancer-Activated Chemotherapy and Photodynamic Therapy to Overcome Drug Resistant Cancers
Pt complexes are commonly used to treat cancer. To reduce their side effects and improve their pharmacological properties, Pt complexes are being developed as prodrug candidates that are activated by reduction in cancer cells. Concomitantly, Ru polypyridine complexes have gained much attention as ph...
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| Veröffentlicht in: | Angewandte Chemie International Edition 2020-04, Vol.59 (18), p.7069-7075 |
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| creator | Karges, Johannes Yempala, Thirumal Tharaud, Mickaël Gibson, Dan Gasser, Gilles |
| description | Pt
complexes are commonly used to treat cancer. To reduce their side effects and improve their pharmacological properties, Pt
complexes are being developed as prodrug candidates that are activated by reduction in cancer cells. Concomitantly, Ru
polypyridine complexes have gained much attention as photosensitizers for use in photodynamic therapy due to their attractive characteristics. In this article, a novel Pt
-Ru
conjugate, which combines cancer activated chemotherapy with PDT, is presented. Upon entering the cancer cell, the Pt
centre is reduced to Pt
and the axial ligands including the Ru
complex and phenylbutyrate are released. As each component has its individual targets, the conjugate exerts a multi-target and multi-action effect with (photo-)cytotoxicity values upon irradiation up to 595 nm in the low nanomolar range in various (drug resistant) 2D monolayer cancer cells and 3D multicellular tumour spheroids. |
| doi_str_mv | 10.1002/anie.201916400 |
| format | Article |
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complexes are commonly used to treat cancer. To reduce their side effects and improve their pharmacological properties, Pt
complexes are being developed as prodrug candidates that are activated by reduction in cancer cells. Concomitantly, Ru
polypyridine complexes have gained much attention as photosensitizers for use in photodynamic therapy due to their attractive characteristics. In this article, a novel Pt
-Ru
conjugate, which combines cancer activated chemotherapy with PDT, is presented. Upon entering the cancer cell, the Pt
centre is reduced to Pt
and the axial ligands including the Ru
complex and phenylbutyrate are released. As each component has its individual targets, the conjugate exerts a multi-target and multi-action effect with (photo-)cytotoxicity values upon irradiation up to 595 nm in the low nanomolar range in various (drug resistant) 2D monolayer cancer cells and 3D multicellular tumour spheroids.</description><identifier>ISSN: 1433-7851</identifier><identifier>EISSN: 1521-3773</identifier><identifier>DOI: 10.1002/anie.201916400</identifier><identifier>PMID: 32017379</identifier><language>eng</language><publisher>Germany</publisher><subject>Antineoplastic Agents - chemical synthesis ; Antineoplastic Agents - chemistry ; Antineoplastic Agents - pharmacology ; Cell Line ; Cell Proliferation - drug effects ; Cell Survival - drug effects ; Coordination Complexes - chemical synthesis ; Coordination Complexes - chemistry ; Coordination Complexes - pharmacology ; Drug Resistance, Neoplasm - drug effects ; Drug Screening Assays, Antitumor ; Drug Therapy, Combination ; Humans ; Infrared Rays ; Molecular Structure ; Photochemotherapy ; Photosensitizing Agents - chemical synthesis ; Photosensitizing Agents - chemistry ; Photosensitizing Agents - pharmacology ; Platinum - chemistry ; Platinum - pharmacology ; Ruthenium - chemistry ; Ruthenium - pharmacology</subject><ispartof>Angewandte Chemie International Edition, 2020-04, Vol.59 (18), p.7069-7075</ispartof><rights>2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c192t-742e746fe251ddfa6c6f7da70769e6f410d366c1a5bde60930993e21c5b744373</citedby><cites>FETCH-LOGICAL-c192t-742e746fe251ddfa6c6f7da70769e6f410d366c1a5bde60930993e21c5b744373</cites><orcidid>0000-0002-4244-5097 ; 0000-0001-5258-0260</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32017379$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Karges, Johannes</creatorcontrib><creatorcontrib>Yempala, Thirumal</creatorcontrib><creatorcontrib>Tharaud, Mickaël</creatorcontrib><creatorcontrib>Gibson, Dan</creatorcontrib><creatorcontrib>Gasser, Gilles</creatorcontrib><title>A Multi-action and Multi-target Ru II -Pt IV Conjugate Combining Cancer-Activated Chemotherapy and Photodynamic Therapy to Overcome Drug Resistant Cancers</title><title>Angewandte Chemie International Edition</title><addtitle>Angew Chem Int Ed Engl</addtitle><description>Pt
complexes are commonly used to treat cancer. To reduce their side effects and improve their pharmacological properties, Pt
complexes are being developed as prodrug candidates that are activated by reduction in cancer cells. Concomitantly, Ru
polypyridine complexes have gained much attention as photosensitizers for use in photodynamic therapy due to their attractive characteristics. In this article, a novel Pt
-Ru
conjugate, which combines cancer activated chemotherapy with PDT, is presented. Upon entering the cancer cell, the Pt
centre is reduced to Pt
and the axial ligands including the Ru
complex and phenylbutyrate are released. As each component has its individual targets, the conjugate exerts a multi-target and multi-action effect with (photo-)cytotoxicity values upon irradiation up to 595 nm in the low nanomolar range in various (drug resistant) 2D monolayer cancer cells and 3D multicellular tumour spheroids.</description><subject>Antineoplastic Agents - chemical synthesis</subject><subject>Antineoplastic Agents - chemistry</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Cell Line</subject><subject>Cell Proliferation - drug effects</subject><subject>Cell Survival - drug effects</subject><subject>Coordination Complexes - chemical synthesis</subject><subject>Coordination Complexes - chemistry</subject><subject>Coordination Complexes - pharmacology</subject><subject>Drug Resistance, Neoplasm - drug effects</subject><subject>Drug Screening Assays, Antitumor</subject><subject>Drug Therapy, Combination</subject><subject>Humans</subject><subject>Infrared Rays</subject><subject>Molecular Structure</subject><subject>Photochemotherapy</subject><subject>Photosensitizing Agents - chemical synthesis</subject><subject>Photosensitizing Agents - chemistry</subject><subject>Photosensitizing Agents - pharmacology</subject><subject>Platinum - chemistry</subject><subject>Platinum - pharmacology</subject><subject>Ruthenium - chemistry</subject><subject>Ruthenium - pharmacology</subject><issn>1433-7851</issn><issn>1521-3773</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kF1PwjAUhhujEURvvTT9A8N23Vp2SebXEgyEoLdL155BCetI15HwV_y1DplcnTfn_bh4EHqkZEwJCZ-lNTAOCU0ojwi5QkMahzRgQrDrTkeMBWIS0wG6a5ptl59MCL9FA9Y1BBPJEP1M8We78yaQypvaYml1__DSrcHjZYuzDAcLj7NvnNZ2266lh05VhbHGrnEqrQIXTLv-oXM0TjdQ1X4DTu6Pf3uLTe1rfbSyMgqvesPXeH4Ap-oK8Itr13gJjWm8tL5fbO7RTSl3DTz0d4S-3l5X6Ucwm79n6XQWKJqEPhBRCCLiJYQx1bqUXPFSaCmI4AnwMqJEM84VlXGhgZOEkSRhEFIVFyKKmGAjND7vKlc3jYMy3ztTSXfMKclPkPMT5PwCuSs8nQv7tqhAX-L_VNkv3315hQ</recordid><startdate>20200427</startdate><enddate>20200427</enddate><creator>Karges, Johannes</creator><creator>Yempala, Thirumal</creator><creator>Tharaud, Mickaël</creator><creator>Gibson, Dan</creator><creator>Gasser, Gilles</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><orcidid>https://orcid.org/0000-0002-4244-5097</orcidid><orcidid>https://orcid.org/0000-0001-5258-0260</orcidid></search><sort><creationdate>20200427</creationdate><title>A Multi-action and Multi-target Ru II -Pt IV Conjugate Combining Cancer-Activated Chemotherapy and Photodynamic Therapy to Overcome Drug Resistant Cancers</title><author>Karges, Johannes ; Yempala, Thirumal ; Tharaud, Mickaël ; Gibson, Dan ; Gasser, Gilles</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c192t-742e746fe251ddfa6c6f7da70769e6f410d366c1a5bde60930993e21c5b744373</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Antineoplastic Agents - chemical synthesis</topic><topic>Antineoplastic Agents - chemistry</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Cell Line</topic><topic>Cell Proliferation - drug effects</topic><topic>Cell Survival - drug effects</topic><topic>Coordination Complexes - chemical synthesis</topic><topic>Coordination Complexes - chemistry</topic><topic>Coordination Complexes - pharmacology</topic><topic>Drug Resistance, Neoplasm - drug effects</topic><topic>Drug Screening Assays, Antitumor</topic><topic>Drug Therapy, Combination</topic><topic>Humans</topic><topic>Infrared Rays</topic><topic>Molecular Structure</topic><topic>Photochemotherapy</topic><topic>Photosensitizing Agents - chemical synthesis</topic><topic>Photosensitizing Agents - chemistry</topic><topic>Photosensitizing Agents - pharmacology</topic><topic>Platinum - chemistry</topic><topic>Platinum - pharmacology</topic><topic>Ruthenium - chemistry</topic><topic>Ruthenium - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Karges, Johannes</creatorcontrib><creatorcontrib>Yempala, Thirumal</creatorcontrib><creatorcontrib>Tharaud, Mickaël</creatorcontrib><creatorcontrib>Gibson, Dan</creatorcontrib><creatorcontrib>Gasser, Gilles</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Angewandte Chemie International Edition</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Karges, Johannes</au><au>Yempala, Thirumal</au><au>Tharaud, Mickaël</au><au>Gibson, Dan</au><au>Gasser, Gilles</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Multi-action and Multi-target Ru II -Pt IV Conjugate Combining Cancer-Activated Chemotherapy and Photodynamic Therapy to Overcome Drug Resistant Cancers</atitle><jtitle>Angewandte Chemie International Edition</jtitle><addtitle>Angew Chem Int Ed Engl</addtitle><date>2020-04-27</date><risdate>2020</risdate><volume>59</volume><issue>18</issue><spage>7069</spage><epage>7075</epage><pages>7069-7075</pages><issn>1433-7851</issn><eissn>1521-3773</eissn><abstract>Pt
complexes are commonly used to treat cancer. To reduce their side effects and improve their pharmacological properties, Pt
complexes are being developed as prodrug candidates that are activated by reduction in cancer cells. Concomitantly, Ru
polypyridine complexes have gained much attention as photosensitizers for use in photodynamic therapy due to their attractive characteristics. In this article, a novel Pt
-Ru
conjugate, which combines cancer activated chemotherapy with PDT, is presented. Upon entering the cancer cell, the Pt
centre is reduced to Pt
and the axial ligands including the Ru
complex and phenylbutyrate are released. As each component has its individual targets, the conjugate exerts a multi-target and multi-action effect with (photo-)cytotoxicity values upon irradiation up to 595 nm in the low nanomolar range in various (drug resistant) 2D monolayer cancer cells and 3D multicellular tumour spheroids.</abstract><cop>Germany</cop><pmid>32017379</pmid><doi>10.1002/anie.201916400</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0002-4244-5097</orcidid><orcidid>https://orcid.org/0000-0001-5258-0260</orcidid></addata></record> |
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| identifier | ISSN: 1433-7851 |
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| source | MEDLINE; Wiley Online Library All Journals |
| subjects | Antineoplastic Agents - chemical synthesis Antineoplastic Agents - chemistry Antineoplastic Agents - pharmacology Cell Line Cell Proliferation - drug effects Cell Survival - drug effects Coordination Complexes - chemical synthesis Coordination Complexes - chemistry Coordination Complexes - pharmacology Drug Resistance, Neoplasm - drug effects Drug Screening Assays, Antitumor Drug Therapy, Combination Humans Infrared Rays Molecular Structure Photochemotherapy Photosensitizing Agents - chemical synthesis Photosensitizing Agents - chemistry Photosensitizing Agents - pharmacology Platinum - chemistry Platinum - pharmacology Ruthenium - chemistry Ruthenium - pharmacology |
| title | A Multi-action and Multi-target Ru II -Pt IV Conjugate Combining Cancer-Activated Chemotherapy and Photodynamic Therapy to Overcome Drug Resistant Cancers |
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