Red‐Light‐Controlled Release of Drug–Ru Complex Conjugates from Metallopolymer Micelles for Phototherapy in Hypoxic Tumor Environments
Traditional photodynamic phototherapy is not efficient for anticancer treatment because solid tumors have a hypoxic microenvironment. The development of photoactivated chemotherapy based on photoresponsive polymers that can be activated by light in the “therapeutic window” would enable new approache...
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| Veröffentlicht in: | Advanced functional materials 2018-09, Vol.28 (39), p.n/a |
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| creator | Sun, Wen Wen, Yan Thiramanas, Raweewan Chen, Mingjia Han, Jianxiong Gong, Ningqiang Wagner, Manfred Jiang, Shuai Meijer, Michael S. Bonnet, Sylvestre Butt, Hans‐Jürgen Mailänder, Volker Liang, Xing‐Jie Wu, Si |
| description | Traditional photodynamic phototherapy is not efficient for anticancer treatment because solid tumors have a hypoxic microenvironment. The development of photoactivated chemotherapy based on photoresponsive polymers that can be activated by light in the “therapeutic window” would enable new approaches for basic research and allow for anticancer phototherapy in hypoxic conditions. This work synthesizes a novel Ru‐containing block copolymer for photoactivated chemotherapy in hypoxic tumor environment. The polymer has a hydrophilic poly(ethylene glycol) block and a hydrophobic Ru‐containing block, which contains red‐light‐cleavable (650–680 nm) drug–Ru complex conjugates. The block copolymer self‐assembles into micelles, which can be efficiently taken up by cancer cells. Red light induces release of the drug–Ru complex conjugates from the micelles and this process is oxygen independent. The released conjugates inhibit tumor cell growth even in hypoxic tumor environment. Furthermore, the Ru‐containing polymer for photoactivated chemotherapy in a tumor‐bearing mouse model is applied. Photoactivated chemotherapy of the polymer micelles demonstrates efficient tumor growth inhibition. In addition, the polymer micelles do not cause any toxic side effects to mice during the treatment, demonstrating good biocompatibility of the system to the blood and healthy tissues. The novel red‐light‐responsive Ru‐containing polymer provides a new platform for phototherapy against hypoxic tumors.
Amphiphilic metallopolymers, which contain photocleavable drug–Ru complex conjugates, self‐assemble into micelles. The micelles are biocompatible and carry the conjugates into tumor cells. Subsequent red light irradiation induces intracellular release of the drug–Ru complex conjugates. Because the photoinduced release is oxygen‐independent, the novel metallopolymer provides a new platform for phototherapy against hypoxic tumors in vivo. |
| doi_str_mv | 10.1002/adfm.201804227 |
| format | Article |
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Amphiphilic metallopolymers, which contain photocleavable drug–Ru complex conjugates, self‐assemble into micelles. The micelles are biocompatible and carry the conjugates into tumor cells. Subsequent red light irradiation induces intracellular release of the drug–Ru complex conjugates. Because the photoinduced release is oxygen‐independent, the novel metallopolymer provides a new platform for phototherapy against hypoxic tumors in vivo.</description><identifier>ISSN: 1616-301X</identifier><identifier>EISSN: 1616-3028</identifier><identifier>DOI: 10.1002/adfm.201804227</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc</publisher><subject>Addition polymerization ; Biocompatibility ; Block copolymers ; Cancer ; Chemotherapy ; Conjugates ; Controlled release ; Hypoxia ; hypoxic tumors ; Light therapy ; Materials science ; metallopolymers ; Micelles ; phototherapy ; Polyethylene glycol ; Polymers ; red light ; ruthenium ; Ruthenium compounds ; Side effects ; Tumors</subject><ispartof>Advanced functional materials, 2018-09, Vol.28 (39), p.n/a</ispartof><rights>2018 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3577-50883023802dc5c8d0d3aef4e924e237c82501cf848ce503429323a52cd64c783</citedby><cites>FETCH-LOGICAL-c3577-50883023802dc5c8d0d3aef4e924e237c82501cf848ce503429323a52cd64c783</cites><orcidid>0000-0003-4316-5350</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%2Fadfm.201804227$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fadfm.201804227$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids></links><search><creatorcontrib>Sun, Wen</creatorcontrib><creatorcontrib>Wen, Yan</creatorcontrib><creatorcontrib>Thiramanas, Raweewan</creatorcontrib><creatorcontrib>Chen, Mingjia</creatorcontrib><creatorcontrib>Han, Jianxiong</creatorcontrib><creatorcontrib>Gong, Ningqiang</creatorcontrib><creatorcontrib>Wagner, Manfred</creatorcontrib><creatorcontrib>Jiang, Shuai</creatorcontrib><creatorcontrib>Meijer, Michael S.</creatorcontrib><creatorcontrib>Bonnet, Sylvestre</creatorcontrib><creatorcontrib>Butt, Hans‐Jürgen</creatorcontrib><creatorcontrib>Mailänder, Volker</creatorcontrib><creatorcontrib>Liang, Xing‐Jie</creatorcontrib><creatorcontrib>Wu, Si</creatorcontrib><title>Red‐Light‐Controlled Release of Drug–Ru Complex Conjugates from Metallopolymer Micelles for Phototherapy in Hypoxic Tumor Environments</title><title>Advanced functional materials</title><description>Traditional photodynamic phototherapy is not efficient for anticancer treatment because solid tumors have a hypoxic microenvironment. The development of photoactivated chemotherapy based on photoresponsive polymers that can be activated by light in the “therapeutic window” would enable new approaches for basic research and allow for anticancer phototherapy in hypoxic conditions. This work synthesizes a novel Ru‐containing block copolymer for photoactivated chemotherapy in hypoxic tumor environment. The polymer has a hydrophilic poly(ethylene glycol) block and a hydrophobic Ru‐containing block, which contains red‐light‐cleavable (650–680 nm) drug–Ru complex conjugates. The block copolymer self‐assembles into micelles, which can be efficiently taken up by cancer cells. Red light induces release of the drug–Ru complex conjugates from the micelles and this process is oxygen independent. The released conjugates inhibit tumor cell growth even in hypoxic tumor environment. Furthermore, the Ru‐containing polymer for photoactivated chemotherapy in a tumor‐bearing mouse model is applied. Photoactivated chemotherapy of the polymer micelles demonstrates efficient tumor growth inhibition. In addition, the polymer micelles do not cause any toxic side effects to mice during the treatment, demonstrating good biocompatibility of the system to the blood and healthy tissues. The novel red‐light‐responsive Ru‐containing polymer provides a new platform for phototherapy against hypoxic tumors.
Amphiphilic metallopolymers, which contain photocleavable drug–Ru complex conjugates, self‐assemble into micelles. The micelles are biocompatible and carry the conjugates into tumor cells. Subsequent red light irradiation induces intracellular release of the drug–Ru complex conjugates. Because the photoinduced release is oxygen‐independent, the novel metallopolymer provides a new platform for phototherapy against hypoxic tumors in vivo.</description><subject>Addition polymerization</subject><subject>Biocompatibility</subject><subject>Block copolymers</subject><subject>Cancer</subject><subject>Chemotherapy</subject><subject>Conjugates</subject><subject>Controlled release</subject><subject>Hypoxia</subject><subject>hypoxic tumors</subject><subject>Light therapy</subject><subject>Materials science</subject><subject>metallopolymers</subject><subject>Micelles</subject><subject>phototherapy</subject><subject>Polyethylene glycol</subject><subject>Polymers</subject><subject>red light</subject><subject>ruthenium</subject><subject>Ruthenium compounds</subject><subject>Side effects</subject><subject>Tumors</subject><issn>1616-301X</issn><issn>1616-3028</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNqFUMtKw0AUDaJgrW5dD7hunUfSTJYlba3QopQK7sIwuWlTJpk4k2iz6we4EPzDfolTKnXp3ZwL53G5x_NuCe4TjOm9SLOiTzHh2Kc0PPM6ZEAGPYYpPz_t5PXSu7J2gzEJQ-Z3vM8FpPvd1yxfrWuHsS5ro5WCFC1AgbCAdIZGplntd9-LBsW6qBRsHZabZiVqsCgzukBzqIVSutKqLcCgeS7BhThSG_S81rWu12BE1aK8RNO20ttcomVTOHZcvudGlwWUtb32LjKhLNz8Ytd7mYyX8bQ3e3p4jIeznmRBGPYCzLl7i3FMUxlInuKUCch8iKgPlIWS0wATmXGfSwgw82nEKBMBlenAlyFnXe_umFsZ_daArZONbkzpTiaUHCaKotCp-keVNNpaA1lSmbwQpk0ITg6NJ4fGk1PjzhAdDR-5gvYfdTIcTeZ_3h_4GYmm</recordid><startdate>20180926</startdate><enddate>20180926</enddate><creator>Sun, Wen</creator><creator>Wen, Yan</creator><creator>Thiramanas, Raweewan</creator><creator>Chen, Mingjia</creator><creator>Han, Jianxiong</creator><creator>Gong, Ningqiang</creator><creator>Wagner, Manfred</creator><creator>Jiang, Shuai</creator><creator>Meijer, Michael S.</creator><creator>Bonnet, Sylvestre</creator><creator>Butt, Hans‐Jürgen</creator><creator>Mailänder, Volker</creator><creator>Liang, Xing‐Jie</creator><creator>Wu, Si</creator><general>Wiley Subscription Services, Inc</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7SP</scope><scope>7SR</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>JG9</scope><scope>L7M</scope><orcidid>https://orcid.org/0000-0003-4316-5350</orcidid></search><sort><creationdate>20180926</creationdate><title>Red‐Light‐Controlled Release of Drug–Ru Complex Conjugates from Metallopolymer Micelles for Phototherapy in Hypoxic Tumor Environments</title><author>Sun, Wen ; Wen, Yan ; Thiramanas, Raweewan ; Chen, Mingjia ; Han, Jianxiong ; Gong, Ningqiang ; Wagner, Manfred ; Jiang, Shuai ; Meijer, Michael S. ; Bonnet, Sylvestre ; Butt, Hans‐Jürgen ; Mailänder, Volker ; Liang, Xing‐Jie ; Wu, Si</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3577-50883023802dc5c8d0d3aef4e924e237c82501cf848ce503429323a52cd64c783</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Addition polymerization</topic><topic>Biocompatibility</topic><topic>Block copolymers</topic><topic>Cancer</topic><topic>Chemotherapy</topic><topic>Conjugates</topic><topic>Controlled release</topic><topic>Hypoxia</topic><topic>hypoxic tumors</topic><topic>Light therapy</topic><topic>Materials science</topic><topic>metallopolymers</topic><topic>Micelles</topic><topic>phototherapy</topic><topic>Polyethylene glycol</topic><topic>Polymers</topic><topic>red light</topic><topic>ruthenium</topic><topic>Ruthenium compounds</topic><topic>Side effects</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sun, Wen</creatorcontrib><creatorcontrib>Wen, Yan</creatorcontrib><creatorcontrib>Thiramanas, Raweewan</creatorcontrib><creatorcontrib>Chen, Mingjia</creatorcontrib><creatorcontrib>Han, Jianxiong</creatorcontrib><creatorcontrib>Gong, Ningqiang</creatorcontrib><creatorcontrib>Wagner, Manfred</creatorcontrib><creatorcontrib>Jiang, Shuai</creatorcontrib><creatorcontrib>Meijer, Michael S.</creatorcontrib><creatorcontrib>Bonnet, Sylvestre</creatorcontrib><creatorcontrib>Butt, Hans‐Jürgen</creatorcontrib><creatorcontrib>Mailänder, Volker</creatorcontrib><creatorcontrib>Liang, Xing‐Jie</creatorcontrib><creatorcontrib>Wu, Si</creatorcontrib><collection>CrossRef</collection><collection>Electronics & Communications Abstracts</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>Advanced functional materials</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sun, Wen</au><au>Wen, Yan</au><au>Thiramanas, Raweewan</au><au>Chen, Mingjia</au><au>Han, Jianxiong</au><au>Gong, Ningqiang</au><au>Wagner, Manfred</au><au>Jiang, Shuai</au><au>Meijer, Michael S.</au><au>Bonnet, Sylvestre</au><au>Butt, Hans‐Jürgen</au><au>Mailänder, Volker</au><au>Liang, Xing‐Jie</au><au>Wu, Si</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Red‐Light‐Controlled Release of Drug–Ru Complex Conjugates from Metallopolymer Micelles for Phototherapy in Hypoxic Tumor Environments</atitle><jtitle>Advanced functional materials</jtitle><date>2018-09-26</date><risdate>2018</risdate><volume>28</volume><issue>39</issue><epage>n/a</epage><issn>1616-301X</issn><eissn>1616-3028</eissn><abstract>Traditional photodynamic phototherapy is not efficient for anticancer treatment because solid tumors have a hypoxic microenvironment. The development of photoactivated chemotherapy based on photoresponsive polymers that can be activated by light in the “therapeutic window” would enable new approaches for basic research and allow for anticancer phototherapy in hypoxic conditions. This work synthesizes a novel Ru‐containing block copolymer for photoactivated chemotherapy in hypoxic tumor environment. The polymer has a hydrophilic poly(ethylene glycol) block and a hydrophobic Ru‐containing block, which contains red‐light‐cleavable (650–680 nm) drug–Ru complex conjugates. The block copolymer self‐assembles into micelles, which can be efficiently taken up by cancer cells. Red light induces release of the drug–Ru complex conjugates from the micelles and this process is oxygen independent. The released conjugates inhibit tumor cell growth even in hypoxic tumor environment. Furthermore, the Ru‐containing polymer for photoactivated chemotherapy in a tumor‐bearing mouse model is applied. Photoactivated chemotherapy of the polymer micelles demonstrates efficient tumor growth inhibition. In addition, the polymer micelles do not cause any toxic side effects to mice during the treatment, demonstrating good biocompatibility of the system to the blood and healthy tissues. The novel red‐light‐responsive Ru‐containing polymer provides a new platform for phototherapy against hypoxic tumors.
Amphiphilic metallopolymers, which contain photocleavable drug–Ru complex conjugates, self‐assemble into micelles. The micelles are biocompatible and carry the conjugates into tumor cells. Subsequent red light irradiation induces intracellular release of the drug–Ru complex conjugates. Because the photoinduced release is oxygen‐independent, the novel metallopolymer provides a new platform for phototherapy against hypoxic tumors in vivo.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc</pub><doi>10.1002/adfm.201804227</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0003-4316-5350</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Addition polymerization Biocompatibility Block copolymers Cancer Chemotherapy Conjugates Controlled release Hypoxia hypoxic tumors Light therapy Materials science metallopolymers Micelles phototherapy Polyethylene glycol Polymers red light ruthenium Ruthenium compounds Side effects Tumors |
| title | Red‐Light‐Controlled Release of Drug–Ru Complex Conjugates from Metallopolymer Micelles for Phototherapy in Hypoxic Tumor Environments |
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