ROS‐Responsive N‐Alkylaminoferrocenes for Cancer‐Cell‐Specific Targeting of Mitochondria
Mitochondrial membrane potential is more negative in cancer cells than in normal cells, allowing cancer targeting by delocalized lipophilic cations (DLCs). However, as the difference is rather small, these drugs affect also normal cells. Now a concept of pro‐DLCs is proposed based on an N‐alkylamino...
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| Veröffentlicht in: | Angewandte Chemie 2018-09, Vol.130 (37), p.12119-12122 |
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| creator | Reshetnikov, Viktor Daum, Steffen Janko, Christina Karawacka, Weronika Tietze, Rainer Alexiou, Christoph Paryzhak, Solomiya Dumych, Tetiana Bilyy, Rostyslav Tripal, Philipp Schmid, Benjamin Palmisano, Ralf Mokhir, Andriy |
| description | Mitochondrial membrane potential is more negative in cancer cells than in normal cells, allowing cancer targeting by delocalized lipophilic cations (DLCs). However, as the difference is rather small, these drugs affect also normal cells. Now a concept of pro‐DLCs is proposed based on an N‐alkylaminoferrocene structure. These prodrugs are activated by the reaction with reactive oxygen species (ROS) forming ferrocenium‐based DLCs. Since ROS are overproduced in cancer, the high‐efficiency cancer‐cell‐specific targeting of mitochondria could be achieved as demonstrated by fluorescence microscopy in combination with two fluorogenic pro‐DLCs in vitro and in vivo. We prepared a conjugate of another pro‐DLC with a clinically approved drug carboplatin and confirmed that its accumulation in mitochondria was higher than that of the free drug. This was reflected in the substantially higher anticancer effect of the conjugate.
Ein kleiner Freund: Ein Platinkomplex mit N‐Alkylaminoferrocen‐Einheit wurde entwickelt, der unter krebsspezifischen Bedingungen aktiviert wird und auf Mitochondrien abzielt. |
| doi_str_mv | 10.1002/ange.201805955 |
| format | Article |
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Ein kleiner Freund: Ein Platinkomplex mit N‐Alkylaminoferrocen‐Einheit wurde entwickelt, der unter krebsspezifischen Bedingungen aktiviert wird und auf Mitochondrien abzielt.</description><subject>Aminoferrocen</subject><subject>Anticancer properties</subject><subject>Cancer</subject><subject>Carboplatin</subject><subject>Cations</subject><subject>Chemical compounds</subject><subject>Chemistry</subject><subject>Conjugates</subject><subject>Drugs</subject><subject>Fluorescence</subject><subject>Fluorescence microscopy</subject><subject>Krebs</subject><subject>Lipophilic</subject><subject>Membrane potential</subject><subject>Mitochondria</subject><subject>Mitochondrien</subject><subject>Prodrugs</subject><subject>Reactive oxygen species</subject><subject>Reaktive Sauerstoffspezies</subject><subject>Tumortherapeutische Prodrugs</subject><issn>0044-8249</issn><issn>1521-3757</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNqFkMFOAjEURRujiYhuXU_ievC1M51pl2SCaIKQAK7HTn3F4jDFFjTs_AS_0S9xCEaXrm5ecs59ySXkkkKPArBr1Sywx4AK4JLzI9KhnNE4yXl-TDoAaRoLlspTchbCEgAylssOeZxOZl8fn1MMa9cE-4bRuD379cuuVivbOIPeO40Nhsg4HxWq0ehbosC6bmO2Rm2N1dFc-QVubLOInInu7cbpZ9c8eavOyYlRdcCLn-ySh5vBvLiNR5PhXdEfxZpmjMeGYaJYJbMKUsZMzplg1AA10nCt04TSpEq4AglGaIkIilaCSgQhBDUKky65OvSuvXvdYtiUS7f1TfuyZCAlyzIq8pbqHSjtXQgeTbn2dqX8rqRQ7lcs9yuWvyu2gjwI77bG3T902R8PB3_uN7_Eeps</recordid><startdate>20180910</startdate><enddate>20180910</enddate><creator>Reshetnikov, Viktor</creator><creator>Daum, Steffen</creator><creator>Janko, Christina</creator><creator>Karawacka, Weronika</creator><creator>Tietze, Rainer</creator><creator>Alexiou, Christoph</creator><creator>Paryzhak, Solomiya</creator><creator>Dumych, Tetiana</creator><creator>Bilyy, Rostyslav</creator><creator>Tripal, Philipp</creator><creator>Schmid, Benjamin</creator><creator>Palmisano, Ralf</creator><creator>Mokhir, Andriy</creator><general>Wiley Subscription Services, Inc</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7SR</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>JG9</scope><scope>L7M</scope><orcidid>https://orcid.org/0000-0002-9079-5569</orcidid></search><sort><creationdate>20180910</creationdate><title>ROS‐Responsive N‐Alkylaminoferrocenes for Cancer‐Cell‐Specific Targeting of Mitochondria</title><author>Reshetnikov, Viktor ; Daum, Steffen ; Janko, Christina ; Karawacka, Weronika ; Tietze, Rainer ; Alexiou, Christoph ; Paryzhak, Solomiya ; Dumych, Tetiana ; Bilyy, Rostyslav ; Tripal, Philipp ; Schmid, Benjamin ; Palmisano, Ralf ; Mokhir, Andriy</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1625-f2e3a2b96b0422f752821f01f9f5cc43113b35a090f8c9ee0a1b819e08881fae3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Aminoferrocen</topic><topic>Anticancer properties</topic><topic>Cancer</topic><topic>Carboplatin</topic><topic>Cations</topic><topic>Chemical compounds</topic><topic>Chemistry</topic><topic>Conjugates</topic><topic>Drugs</topic><topic>Fluorescence</topic><topic>Fluorescence microscopy</topic><topic>Krebs</topic><topic>Lipophilic</topic><topic>Membrane potential</topic><topic>Mitochondria</topic><topic>Mitochondrien</topic><topic>Prodrugs</topic><topic>Reactive oxygen species</topic><topic>Reaktive Sauerstoffspezies</topic><topic>Tumortherapeutische Prodrugs</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Reshetnikov, Viktor</creatorcontrib><creatorcontrib>Daum, Steffen</creatorcontrib><creatorcontrib>Janko, Christina</creatorcontrib><creatorcontrib>Karawacka, Weronika</creatorcontrib><creatorcontrib>Tietze, Rainer</creatorcontrib><creatorcontrib>Alexiou, Christoph</creatorcontrib><creatorcontrib>Paryzhak, Solomiya</creatorcontrib><creatorcontrib>Dumych, Tetiana</creatorcontrib><creatorcontrib>Bilyy, Rostyslav</creatorcontrib><creatorcontrib>Tripal, Philipp</creatorcontrib><creatorcontrib>Schmid, Benjamin</creatorcontrib><creatorcontrib>Palmisano, Ralf</creatorcontrib><creatorcontrib>Mokhir, Andriy</creatorcontrib><collection>CrossRef</collection><collection>Engineered Materials Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Materials Research Database</collection><collection>Advanced Technologies Database with Aerospace</collection><jtitle>Angewandte Chemie</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Reshetnikov, Viktor</au><au>Daum, Steffen</au><au>Janko, Christina</au><au>Karawacka, Weronika</au><au>Tietze, Rainer</au><au>Alexiou, Christoph</au><au>Paryzhak, Solomiya</au><au>Dumych, Tetiana</au><au>Bilyy, Rostyslav</au><au>Tripal, Philipp</au><au>Schmid, Benjamin</au><au>Palmisano, Ralf</au><au>Mokhir, Andriy</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>ROS‐Responsive N‐Alkylaminoferrocenes for Cancer‐Cell‐Specific Targeting of Mitochondria</atitle><jtitle>Angewandte Chemie</jtitle><date>2018-09-10</date><risdate>2018</risdate><volume>130</volume><issue>37</issue><spage>12119</spage><epage>12122</epage><pages>12119-12122</pages><issn>0044-8249</issn><eissn>1521-3757</eissn><abstract>Mitochondrial membrane potential is more negative in cancer cells than in normal cells, allowing cancer targeting by delocalized lipophilic cations (DLCs). However, as the difference is rather small, these drugs affect also normal cells. Now a concept of pro‐DLCs is proposed based on an N‐alkylaminoferrocene structure. These prodrugs are activated by the reaction with reactive oxygen species (ROS) forming ferrocenium‐based DLCs. Since ROS are overproduced in cancer, the high‐efficiency cancer‐cell‐specific targeting of mitochondria could be achieved as demonstrated by fluorescence microscopy in combination with two fluorogenic pro‐DLCs in vitro and in vivo. We prepared a conjugate of another pro‐DLC with a clinically approved drug carboplatin and confirmed that its accumulation in mitochondria was higher than that of the free drug. This was reflected in the substantially higher anticancer effect of the conjugate.
Ein kleiner Freund: Ein Platinkomplex mit N‐Alkylaminoferrocen‐Einheit wurde entwickelt, der unter krebsspezifischen Bedingungen aktiviert wird und auf Mitochondrien abzielt.</abstract><cop>Weinheim</cop><pub>Wiley Subscription Services, Inc</pub><doi>10.1002/ange.201805955</doi><tpages>4</tpages><orcidid>https://orcid.org/0000-0002-9079-5569</orcidid></addata></record> |
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| subjects | Aminoferrocen Anticancer properties Cancer Carboplatin Cations Chemical compounds Chemistry Conjugates Drugs Fluorescence Fluorescence microscopy Krebs Lipophilic Membrane potential Mitochondria Mitochondrien Prodrugs Reactive oxygen species Reaktive Sauerstoffspezies Tumortherapeutische Prodrugs |
| title | ROS‐Responsive N‐Alkylaminoferrocenes for Cancer‐Cell‐Specific Targeting of Mitochondria |
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