Smart Tumor‐Cell‐Derived Microparticles Provide On‐Demand Photosensitizer Synthesis and Hypoxia Relief for Photodynamic Therapy
Positioning essential elements of photodynamic therapy (PDT) near to mitochondria can conquer the rigorous spatiotemporal limitations of reactive oxygen species (ROS) transfer and make considerable differences in PDT. However, precise accumulation of photosensitizer (PS) and oxygen within mitochondr...
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| Veröffentlicht in: | Angewandte Chemie International Edition 2021-11, Vol.60 (48), p.25365-25371 |
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| container_title | Angewandte Chemie International Edition |
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| creator | Zuo, Liping Nie, Weidong Yu, Songmao Zhuang, Wanru Wu, Guanghao Liu, Houli Huang, Lili Shi, Danshu Sui, Xin Li, Yongheng Xie, Hai‐Yan |
| description | Positioning essential elements of photodynamic therapy (PDT) near to mitochondria can conquer the rigorous spatiotemporal limitations of reactive oxygen species (ROS) transfer and make considerable differences in PDT. However, precise accumulation of photosensitizer (PS) and oxygen within mitochondria is still challenging. We simultaneously encapsulated hexyl 5‐aminolevulinate hydrochloride (HAL) and 3‐bromopyruvic acid (3BP) into microparticles collected from X‐ray‐irradiated tumor cells (X‐MP). After systemic administration, the developed HAL/3BP@X‐MP can specifically target and recognize tumor cells, where HAL induces efficient accumulation of PpIX in mitochondria via the intrinsic haem biosynthetic pathway. Meanwhile, 3BP remarkably increases the oxygen supply by inhibiting mitochondrial respiration. The accurate co‐localization and prompt encounter of PpIX and oxygen produce sufficient ROS to directly disrupt mitochondria, resulting in significantly improved PDT outcomes.
Accurate co‐localization of PpIX and O2: HAL and 3BP‐loaded microparticles specifically target and recognize tumor cells, wherein HAL induces the biosynthesis of PpIX in mitochondria and 3BP reduces the mitochondria oxygen consumption. The precise co‐localization of PpIX and O2 produces sufficient singlet oxygen to directly disrupt mitochondria, significantly improving PDT. |
| doi_str_mv | 10.1002/anie.202109258 |
| format | Article |
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Accurate co‐localization of PpIX and O2: HAL and 3BP‐loaded microparticles specifically target and recognize tumor cells, wherein HAL induces the biosynthesis of PpIX in mitochondria and 3BP reduces the mitochondria oxygen consumption. The precise co‐localization of PpIX and O2 produces sufficient singlet oxygen to directly disrupt mitochondria, significantly improving PDT.</description><edition>International ed. in English</edition><identifier>ISSN: 1433-7851</identifier><identifier>EISSN: 1521-3773</identifier><identifier>DOI: 10.1002/anie.202109258</identifier><identifier>PMID: 34528355</identifier><language>eng</language><publisher>Germany: Wiley Subscription Services, Inc</publisher><subject>Accumulation ; accurate delivery ; Animals ; Antineoplastic Agents - chemistry ; Antineoplastic Agents - metabolism ; Antineoplastic Agents - pharmacology ; biosynthesis ; Cell Hypoxia - drug effects ; Cell Line, Tumor ; Cell-Derived Microparticles - chemistry ; Cell-Derived Microparticles - metabolism ; Humans ; Hypoxia ; Localization ; Mice ; Microparticles ; Mitochondria ; Molecular Structure ; Neoplasms, Experimental - drug therapy ; Neoplasms, Experimental - metabolism ; Neoplasms, Experimental - pathology ; Optical Imaging ; Oxygen ; Photochemotherapy ; Photodynamic therapy ; Photosensitizing Agents - chemistry ; Photosensitizing Agents - metabolism ; Photosensitizing Agents - pharmacology ; Reactive oxygen species ; Reactive Oxygen Species - metabolism ; relief hypoxia ; Tumor cells ; Tumors</subject><ispartof>Angewandte Chemie International Edition, 2021-11, Vol.60 (48), p.25365-25371</ispartof><rights>2021 Wiley‐VCH GmbH</rights><rights>2021 Wiley-VCH GmbH.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3738-c6af8c4b5740ddcd5e2feb4bd8f526e4db72d803a300802e91c8975d03a2eeb03</citedby><cites>FETCH-LOGICAL-c3738-c6af8c4b5740ddcd5e2feb4bd8f526e4db72d803a300802e91c8975d03a2eeb03</cites><orcidid>0000-0002-6330-7929</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%2Fanie.202109258$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fanie.202109258$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34528355$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zuo, Liping</creatorcontrib><creatorcontrib>Nie, Weidong</creatorcontrib><creatorcontrib>Yu, Songmao</creatorcontrib><creatorcontrib>Zhuang, Wanru</creatorcontrib><creatorcontrib>Wu, Guanghao</creatorcontrib><creatorcontrib>Liu, Houli</creatorcontrib><creatorcontrib>Huang, Lili</creatorcontrib><creatorcontrib>Shi, Danshu</creatorcontrib><creatorcontrib>Sui, Xin</creatorcontrib><creatorcontrib>Li, Yongheng</creatorcontrib><creatorcontrib>Xie, Hai‐Yan</creatorcontrib><title>Smart Tumor‐Cell‐Derived Microparticles Provide On‐Demand Photosensitizer Synthesis and Hypoxia Relief for Photodynamic Therapy</title><title>Angewandte Chemie International Edition</title><addtitle>Angew Chem Int Ed Engl</addtitle><description>Positioning essential elements of photodynamic therapy (PDT) near to mitochondria can conquer the rigorous spatiotemporal limitations of reactive oxygen species (ROS) transfer and make considerable differences in PDT. However, precise accumulation of photosensitizer (PS) and oxygen within mitochondria is still challenging. We simultaneously encapsulated hexyl 5‐aminolevulinate hydrochloride (HAL) and 3‐bromopyruvic acid (3BP) into microparticles collected from X‐ray‐irradiated tumor cells (X‐MP). After systemic administration, the developed HAL/3BP@X‐MP can specifically target and recognize tumor cells, where HAL induces efficient accumulation of PpIX in mitochondria via the intrinsic haem biosynthetic pathway. Meanwhile, 3BP remarkably increases the oxygen supply by inhibiting mitochondrial respiration. The accurate co‐localization and prompt encounter of PpIX and oxygen produce sufficient ROS to directly disrupt mitochondria, resulting in significantly improved PDT outcomes.
Accurate co‐localization of PpIX and O2: HAL and 3BP‐loaded microparticles specifically target and recognize tumor cells, wherein HAL induces the biosynthesis of PpIX in mitochondria and 3BP reduces the mitochondria oxygen consumption. The precise co‐localization of PpIX and O2 produces sufficient singlet oxygen to directly disrupt mitochondria, significantly improving PDT.</description><subject>Accumulation</subject><subject>accurate delivery</subject><subject>Animals</subject><subject>Antineoplastic Agents - chemistry</subject><subject>Antineoplastic Agents - metabolism</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>biosynthesis</subject><subject>Cell Hypoxia - drug effects</subject><subject>Cell Line, Tumor</subject><subject>Cell-Derived Microparticles - chemistry</subject><subject>Cell-Derived Microparticles - metabolism</subject><subject>Humans</subject><subject>Hypoxia</subject><subject>Localization</subject><subject>Mice</subject><subject>Microparticles</subject><subject>Mitochondria</subject><subject>Molecular Structure</subject><subject>Neoplasms, Experimental - drug therapy</subject><subject>Neoplasms, Experimental - metabolism</subject><subject>Neoplasms, Experimental - pathology</subject><subject>Optical Imaging</subject><subject>Oxygen</subject><subject>Photochemotherapy</subject><subject>Photodynamic therapy</subject><subject>Photosensitizing Agents - chemistry</subject><subject>Photosensitizing Agents - metabolism</subject><subject>Photosensitizing Agents - pharmacology</subject><subject>Reactive oxygen species</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>relief hypoxia</subject><subject>Tumor cells</subject><subject>Tumors</subject><issn>1433-7851</issn><issn>1521-3773</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkDtPwzAQxy0E4lFYGZEl5hTHjmtnROUplYegzJETX1SjJA52CoSJhZ3PyCfBpTxGpjudf_c_-YfQbkyGMSH0QDUGhpTQmKSUyxW0GXMaR0wIthr6hLFISB5voC3v7wMvJRmtow2WcCoZ55vo7bZWrsPTeW3dx-v7GKoqlCNw5hE0vjCFs20ATFGBx9fOPhoN-Kr5YmrVaHw9s5310HjTmRdw-LZvuhl44_Hi9axv7bNR-AYqAyUurVsu6L5RtSnwdAZOtf02WitV5WHnuw7Q3cnxdHwWTa5Oz8eHk6hggsmoGKlSFknORUK0LjQHWkKe5FqWnI4g0bmgWhKmGCGSUEjjQqaC6zChADlhA7S_zG2dfZiD77J7O3dNOJlRnook4UIsqOGSCp_33kGZtc4ETX0Wk2xhPVtYz36th4W979h5XoP-xX80ByBdAk-mgv6fuOzw8vz4L_wTpGWUXg</recordid><startdate>20211122</startdate><enddate>20211122</enddate><creator>Zuo, Liping</creator><creator>Nie, Weidong</creator><creator>Yu, Songmao</creator><creator>Zhuang, Wanru</creator><creator>Wu, Guanghao</creator><creator>Liu, Houli</creator><creator>Huang, Lili</creator><creator>Shi, Danshu</creator><creator>Sui, Xin</creator><creator>Li, Yongheng</creator><creator>Xie, Hai‐Yan</creator><general>Wiley Subscription Services, Inc</general><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>7TM</scope><scope>K9.</scope><orcidid>https://orcid.org/0000-0002-6330-7929</orcidid></search><sort><creationdate>20211122</creationdate><title>Smart Tumor‐Cell‐Derived Microparticles Provide On‐Demand Photosensitizer Synthesis and Hypoxia Relief for Photodynamic Therapy</title><author>Zuo, Liping ; Nie, Weidong ; Yu, Songmao ; Zhuang, Wanru ; Wu, Guanghao ; Liu, Houli ; Huang, Lili ; Shi, Danshu ; Sui, Xin ; Li, Yongheng ; Xie, Hai‐Yan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3738-c6af8c4b5740ddcd5e2feb4bd8f526e4db72d803a300802e91c8975d03a2eeb03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Accumulation</topic><topic>accurate delivery</topic><topic>Animals</topic><topic>Antineoplastic Agents - chemistry</topic><topic>Antineoplastic Agents - metabolism</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>biosynthesis</topic><topic>Cell Hypoxia - drug effects</topic><topic>Cell Line, Tumor</topic><topic>Cell-Derived Microparticles - chemistry</topic><topic>Cell-Derived Microparticles - metabolism</topic><topic>Humans</topic><topic>Hypoxia</topic><topic>Localization</topic><topic>Mice</topic><topic>Microparticles</topic><topic>Mitochondria</topic><topic>Molecular Structure</topic><topic>Neoplasms, Experimental - drug therapy</topic><topic>Neoplasms, Experimental - metabolism</topic><topic>Neoplasms, Experimental - pathology</topic><topic>Optical Imaging</topic><topic>Oxygen</topic><topic>Photochemotherapy</topic><topic>Photodynamic therapy</topic><topic>Photosensitizing Agents - chemistry</topic><topic>Photosensitizing Agents - metabolism</topic><topic>Photosensitizing Agents - pharmacology</topic><topic>Reactive oxygen species</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>relief hypoxia</topic><topic>Tumor cells</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zuo, Liping</creatorcontrib><creatorcontrib>Nie, Weidong</creatorcontrib><creatorcontrib>Yu, Songmao</creatorcontrib><creatorcontrib>Zhuang, Wanru</creatorcontrib><creatorcontrib>Wu, Guanghao</creatorcontrib><creatorcontrib>Liu, Houli</creatorcontrib><creatorcontrib>Huang, Lili</creatorcontrib><creatorcontrib>Shi, Danshu</creatorcontrib><creatorcontrib>Sui, Xin</creatorcontrib><creatorcontrib>Li, Yongheng</creatorcontrib><creatorcontrib>Xie, Hai‐Yan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><jtitle>Angewandte Chemie International Edition</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zuo, Liping</au><au>Nie, Weidong</au><au>Yu, Songmao</au><au>Zhuang, Wanru</au><au>Wu, Guanghao</au><au>Liu, Houli</au><au>Huang, Lili</au><au>Shi, Danshu</au><au>Sui, Xin</au><au>Li, Yongheng</au><au>Xie, Hai‐Yan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Smart Tumor‐Cell‐Derived Microparticles Provide On‐Demand Photosensitizer Synthesis and Hypoxia Relief for Photodynamic Therapy</atitle><jtitle>Angewandte Chemie International Edition</jtitle><addtitle>Angew Chem Int Ed Engl</addtitle><date>2021-11-22</date><risdate>2021</risdate><volume>60</volume><issue>48</issue><spage>25365</spage><epage>25371</epage><pages>25365-25371</pages><issn>1433-7851</issn><eissn>1521-3773</eissn><abstract>Positioning essential elements of photodynamic therapy (PDT) near to mitochondria can conquer the rigorous spatiotemporal limitations of reactive oxygen species (ROS) transfer and make considerable differences in PDT. However, precise accumulation of photosensitizer (PS) and oxygen within mitochondria is still challenging. We simultaneously encapsulated hexyl 5‐aminolevulinate hydrochloride (HAL) and 3‐bromopyruvic acid (3BP) into microparticles collected from X‐ray‐irradiated tumor cells (X‐MP). After systemic administration, the developed HAL/3BP@X‐MP can specifically target and recognize tumor cells, where HAL induces efficient accumulation of PpIX in mitochondria via the intrinsic haem biosynthetic pathway. Meanwhile, 3BP remarkably increases the oxygen supply by inhibiting mitochondrial respiration. The accurate co‐localization and prompt encounter of PpIX and oxygen produce sufficient ROS to directly disrupt mitochondria, resulting in significantly improved PDT outcomes.
Accurate co‐localization of PpIX and O2: HAL and 3BP‐loaded microparticles specifically target and recognize tumor cells, wherein HAL induces the biosynthesis of PpIX in mitochondria and 3BP reduces the mitochondria oxygen consumption. The precise co‐localization of PpIX and O2 produces sufficient singlet oxygen to directly disrupt mitochondria, significantly improving PDT.</abstract><cop>Germany</cop><pub>Wiley Subscription Services, Inc</pub><pmid>34528355</pmid><doi>10.1002/anie.202109258</doi><tpages>7</tpages><edition>International ed. in English</edition><orcidid>https://orcid.org/0000-0002-6330-7929</orcidid></addata></record> |
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| subjects | Accumulation accurate delivery Animals Antineoplastic Agents - chemistry Antineoplastic Agents - metabolism Antineoplastic Agents - pharmacology biosynthesis Cell Hypoxia - drug effects Cell Line, Tumor Cell-Derived Microparticles - chemistry Cell-Derived Microparticles - metabolism Humans Hypoxia Localization Mice Microparticles Mitochondria Molecular Structure Neoplasms, Experimental - drug therapy Neoplasms, Experimental - metabolism Neoplasms, Experimental - pathology Optical Imaging Oxygen Photochemotherapy Photodynamic therapy Photosensitizing Agents - chemistry Photosensitizing Agents - metabolism Photosensitizing Agents - pharmacology Reactive oxygen species Reactive Oxygen Species - metabolism relief hypoxia Tumor cells Tumors |
| title | Smart Tumor‐Cell‐Derived Microparticles Provide On‐Demand Photosensitizer Synthesis and Hypoxia Relief for Photodynamic Therapy |
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