ROS-responsive chitosan-SS31 prodrug for AKI therapy via rapid distribution in the kidney and long-term retention in the renal tubule
The development of drugs with rapid distribution in the kidney and long-term retention in the renal tubule is a breakthrough for enhanced treatment of acute kidney injury (AKI). Here, l-serine-modified chitosan (SC) was synthesized as a potential AKI kidney-targeting agent due to the native cationic...
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| Veröffentlicht in: | Science advances 2020-10, Vol.6 (41) |
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| creator | Liu, Di Shu, Gaofeng Jin, Feiyang Qi, Jing Xu, Xiaoling Du, Yan Yu, Hui Wang, Jun Sun, Mingchen You, Yuchan Zhu, Minxia Chen, Meixuan Zhu, Luwen Shen, Qiying Ying, Xiaoying Lou, Xuefang Jiang, Saiping Du, Yongzhong |
| description | The development of drugs with rapid distribution in the kidney and long-term retention in the renal tubule is a breakthrough for enhanced treatment of acute kidney injury (AKI). Here, l-serine-modified chitosan (SC) was synthesized as a potential AKI kidney-targeting agent due to the native cationic property of chitosan and specific interaction between kidney injury molecule-1 (Kim-1) and serine. Results indicated that SC was rapidly accumulated and long-term retained in ischemia-reperfusion-induced AKI kidneys, especially in renal tubules, which was possibly due to the specific interactions between SC and Kim-1. SC-TK-SS31 was then prepared by conjugating SS31, a mitochondria-targeted antioxidant, to SC via reactive oxygen species (ROS)-sensitive thioketal linker. Because of the effective renal distribution combined with ROS-responsive drug release behavior, the administration of SC-TK-SS31 led to an enhanced therapeutic effect of SS31 by protecting mitochondria from damage and reducing the oxidative stress, inflammation, and cell apoptosis. |
| doi_str_mv | 10.1126/sciadv.abb7422 |
| format | Article |
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Here, l-serine-modified chitosan (SC) was synthesized as a potential AKI kidney-targeting agent due to the native cationic property of chitosan and specific interaction between kidney injury molecule-1 (Kim-1) and serine. Results indicated that SC was rapidly accumulated and long-term retained in ischemia-reperfusion-induced AKI kidneys, especially in renal tubules, which was possibly due to the specific interactions between SC and Kim-1. SC-TK-SS31 was then prepared by conjugating SS31, a mitochondria-targeted antioxidant, to SC via reactive oxygen species (ROS)-sensitive thioketal linker. Because of the effective renal distribution combined with ROS-responsive drug release behavior, the administration of SC-TK-SS31 led to an enhanced therapeutic effect of SS31 by protecting mitochondria from damage and reducing the oxidative stress, inflammation, and cell apoptosis.</description><identifier>ISSN: 2375-2548</identifier><identifier>EISSN: 2375-2548</identifier><identifier>DOI: 10.1126/sciadv.abb7422</identifier><identifier>PMID: 33036968</identifier><language>eng</language><publisher>United States: American Association for the Advancement of Science</publisher><subject>Diseases and Disorders ; Health and Medicine ; Materials Science ; SciAdv r-articles</subject><ispartof>Science advances, 2020-10, Vol.6 (41)</ispartof><rights>Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).</rights><rights>Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). 2020 The Authors</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c390t-73fc7e96a72eaef554dd8f00e4e3f01ff7d600733e4d18d922b537cca44aa1a63</citedby><cites>FETCH-LOGICAL-c390t-73fc7e96a72eaef554dd8f00e4e3f01ff7d600733e4d18d922b537cca44aa1a63</cites><orcidid>0000-0002-1395-0035 ; 0000-0002-9220-6852 ; 0000-0001-6618-5122 ; 0000-0002-2735-834X ; 0000-0003-4563-8510 ; 0000-0002-1600-1740 ; 0000-0002-7472-0495 ; 0000-0002-8442-7073 ; 0000-0002-2734-3252 ; 0000-0001-9394-4403 ; 0000-0002-6415-3458 ; 0000-0002-2137-4517 ; 0000-0002-9481-2901 ; 0000-0001-6656-5969 ; 0000-0002-8944-3865 ; 0000-0001-7982-2020 ; 0000-0001-7082-4361 ; 0000-0001-7420-897X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546709/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546709/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33036968$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liu, Di</creatorcontrib><creatorcontrib>Shu, Gaofeng</creatorcontrib><creatorcontrib>Jin, Feiyang</creatorcontrib><creatorcontrib>Qi, Jing</creatorcontrib><creatorcontrib>Xu, Xiaoling</creatorcontrib><creatorcontrib>Du, Yan</creatorcontrib><creatorcontrib>Yu, Hui</creatorcontrib><creatorcontrib>Wang, Jun</creatorcontrib><creatorcontrib>Sun, Mingchen</creatorcontrib><creatorcontrib>You, Yuchan</creatorcontrib><creatorcontrib>Zhu, Minxia</creatorcontrib><creatorcontrib>Chen, Meixuan</creatorcontrib><creatorcontrib>Zhu, Luwen</creatorcontrib><creatorcontrib>Shen, Qiying</creatorcontrib><creatorcontrib>Ying, Xiaoying</creatorcontrib><creatorcontrib>Lou, Xuefang</creatorcontrib><creatorcontrib>Jiang, Saiping</creatorcontrib><creatorcontrib>Du, Yongzhong</creatorcontrib><title>ROS-responsive chitosan-SS31 prodrug for AKI therapy via rapid distribution in the kidney and long-term retention in the renal tubule</title><title>Science advances</title><addtitle>Sci Adv</addtitle><description>The development of drugs with rapid distribution in the kidney and long-term retention in the renal tubule is a breakthrough for enhanced treatment of acute kidney injury (AKI). Here, l-serine-modified chitosan (SC) was synthesized as a potential AKI kidney-targeting agent due to the native cationic property of chitosan and specific interaction between kidney injury molecule-1 (Kim-1) and serine. Results indicated that SC was rapidly accumulated and long-term retained in ischemia-reperfusion-induced AKI kidneys, especially in renal tubules, which was possibly due to the specific interactions between SC and Kim-1. SC-TK-SS31 was then prepared by conjugating SS31, a mitochondria-targeted antioxidant, to SC via reactive oxygen species (ROS)-sensitive thioketal linker. 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Shu, Gaofeng ; Jin, Feiyang ; Qi, Jing ; Xu, Xiaoling ; Du, Yan ; Yu, Hui ; Wang, Jun ; Sun, Mingchen ; You, Yuchan ; Zhu, Minxia ; Chen, Meixuan ; Zhu, Luwen ; Shen, Qiying ; Ying, Xiaoying ; Lou, Xuefang ; Jiang, Saiping ; Du, Yongzhong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c390t-73fc7e96a72eaef554dd8f00e4e3f01ff7d600733e4d18d922b537cca44aa1a63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Diseases and Disorders</topic><topic>Health and Medicine</topic><topic>Materials Science</topic><topic>SciAdv r-articles</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liu, Di</creatorcontrib><creatorcontrib>Shu, Gaofeng</creatorcontrib><creatorcontrib>Jin, Feiyang</creatorcontrib><creatorcontrib>Qi, Jing</creatorcontrib><creatorcontrib>Xu, Xiaoling</creatorcontrib><creatorcontrib>Du, Yan</creatorcontrib><creatorcontrib>Yu, Hui</creatorcontrib><creatorcontrib>Wang, Jun</creatorcontrib><creatorcontrib>Sun, Mingchen</creatorcontrib><creatorcontrib>You, Yuchan</creatorcontrib><creatorcontrib>Zhu, Minxia</creatorcontrib><creatorcontrib>Chen, Meixuan</creatorcontrib><creatorcontrib>Zhu, Luwen</creatorcontrib><creatorcontrib>Shen, Qiying</creatorcontrib><creatorcontrib>Ying, Xiaoying</creatorcontrib><creatorcontrib>Lou, Xuefang</creatorcontrib><creatorcontrib>Jiang, Saiping</creatorcontrib><creatorcontrib>Du, Yongzhong</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Science advances</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, Di</au><au>Shu, Gaofeng</au><au>Jin, Feiyang</au><au>Qi, Jing</au><au>Xu, Xiaoling</au><au>Du, Yan</au><au>Yu, Hui</au><au>Wang, Jun</au><au>Sun, Mingchen</au><au>You, Yuchan</au><au>Zhu, Minxia</au><au>Chen, Meixuan</au><au>Zhu, Luwen</au><au>Shen, Qiying</au><au>Ying, Xiaoying</au><au>Lou, Xuefang</au><au>Jiang, Saiping</au><au>Du, Yongzhong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>ROS-responsive chitosan-SS31 prodrug for AKI therapy via rapid distribution in the kidney and long-term retention in the renal tubule</atitle><jtitle>Science advances</jtitle><addtitle>Sci Adv</addtitle><date>2020-10-01</date><risdate>2020</risdate><volume>6</volume><issue>41</issue><issn>2375-2548</issn><eissn>2375-2548</eissn><abstract>The development of drugs with rapid distribution in the kidney and long-term retention in the renal tubule is a breakthrough for enhanced treatment of acute kidney injury (AKI). Here, l-serine-modified chitosan (SC) was synthesized as a potential AKI kidney-targeting agent due to the native cationic property of chitosan and specific interaction between kidney injury molecule-1 (Kim-1) and serine. Results indicated that SC was rapidly accumulated and long-term retained in ischemia-reperfusion-induced AKI kidneys, especially in renal tubules, which was possibly due to the specific interactions between SC and Kim-1. SC-TK-SS31 was then prepared by conjugating SS31, a mitochondria-targeted antioxidant, to SC via reactive oxygen species (ROS)-sensitive thioketal linker. Because of the effective renal distribution combined with ROS-responsive drug release behavior, the administration of SC-TK-SS31 led to an enhanced therapeutic effect of SS31 by protecting mitochondria from damage and reducing the oxidative stress, inflammation, and cell apoptosis.</abstract><cop>United States</cop><pub>American Association for the Advancement of Science</pub><pmid>33036968</pmid><doi>10.1126/sciadv.abb7422</doi><orcidid>https://orcid.org/0000-0002-1395-0035</orcidid><orcidid>https://orcid.org/0000-0002-9220-6852</orcidid><orcidid>https://orcid.org/0000-0001-6618-5122</orcidid><orcidid>https://orcid.org/0000-0002-2735-834X</orcidid><orcidid>https://orcid.org/0000-0003-4563-8510</orcidid><orcidid>https://orcid.org/0000-0002-1600-1740</orcidid><orcidid>https://orcid.org/0000-0002-7472-0495</orcidid><orcidid>https://orcid.org/0000-0002-8442-7073</orcidid><orcidid>https://orcid.org/0000-0002-2734-3252</orcidid><orcidid>https://orcid.org/0000-0001-9394-4403</orcidid><orcidid>https://orcid.org/0000-0002-6415-3458</orcidid><orcidid>https://orcid.org/0000-0002-2137-4517</orcidid><orcidid>https://orcid.org/0000-0002-9481-2901</orcidid><orcidid>https://orcid.org/0000-0001-6656-5969</orcidid><orcidid>https://orcid.org/0000-0002-8944-3865</orcidid><orcidid>https://orcid.org/0000-0001-7982-2020</orcidid><orcidid>https://orcid.org/0000-0001-7082-4361</orcidid><orcidid>https://orcid.org/0000-0001-7420-897X</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Diseases and Disorders Health and Medicine Materials Science SciAdv r-articles |
| title | ROS-responsive chitosan-SS31 prodrug for AKI therapy via rapid distribution in the kidney and long-term retention in the renal tubule |
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