Reactive Oxygen Species-Responsive Protein Modification and Its Intracellular Delivery for Targeted Cancer Therapy
Herein we report a convenient chemical approach to reversibly modulate protein (RNase A) function and develop a protein that is responsive to reactive oxygen species (ROS) for targeted cancer therapy. The conjugation of RNase A with 4‐nitrophenyl 4‐(4,4,5,5‐tetramethyl‐1,3,2‐dioxaborolan‐2‐yl) benzy...
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| Veröffentlicht in: | Angewandte Chemie International Edition 2014-12, Vol.53 (49), p.13444-13448 |
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| creator | Wang, Ming Sun, Shuo Neufeld, Caleb I. Perez-Ramirez, Bernardo Xu, Qiaobing |
| description | Herein we report a convenient chemical approach to reversibly modulate protein (RNase A) function and develop a protein that is responsive to reactive oxygen species (ROS) for targeted cancer therapy. The conjugation of RNase A with 4‐nitrophenyl 4‐(4,4,5,5‐tetramethyl‐1,3,2‐dioxaborolan‐2‐yl) benzyl carbonate (NBC) blocks protein lysine and temporarily deactivates the protein. However, the treatment of RNase A–NBC with hydrogen peroxide (one major intracellular ROS) efficiently cleaves the NBC conjugation and restores the RNase A activity. Thus, RNase A–NBC can be reactivated inside tumor cells by high levels of intracellular ROS, thereby restoring the cytotoxicity of RNase A for cancer therapy. Due to higher ROS levels inside tumor cells compared to healthy cells, and the resulting different levels of RNase A–NBC reactivation, RNase A–NBC shows a significant specific cytotoxicity against tumor cells.
Reversible protein function modulation was achieved by a convenient chemical approach. RNase A was equipped with a boronic acid group (RNase A–NBC) that responds to reactive oxygen species (ROS). This complex shows cytotoxicity in the presence of ROS, as for example in cancer cells, whereas healthy cells are only affected at significantly higher concentrations. |
| doi_str_mv | 10.1002/anie.201407234 |
| format | Article |
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Reversible protein function modulation was achieved by a convenient chemical approach. RNase A was equipped with a boronic acid group (RNase A–NBC) that responds to reactive oxygen species (ROS). This complex shows cytotoxicity in the presence of ROS, as for example in cancer cells, whereas healthy cells are only affected at significantly higher concentrations.</description><edition>International ed. in English</edition><identifier>ISSN: 1433-7851</identifier><identifier>EISSN: 1521-3773</identifier><identifier>DOI: 10.1002/anie.201407234</identifier><identifier>PMID: 25287050</identifier><identifier>CODEN: ACIEAY</identifier><language>eng</language><publisher>Weinheim: WILEY-VCH Verlag</publisher><subject>Benzyl Compounds - chemistry ; Benzyl Compounds - metabolism ; Cancer ; Cancer therapies ; Carbonates ; Carbonates - chemistry ; Carbonates - metabolism ; Cell Line, Tumor ; Conjugation ; Cytotoxicity ; drug delivery ; Enzyme Therapy ; Humans ; Hydrogen peroxide ; Lysine ; Modulation ; nanoparticles ; Neoplasms - drug therapy ; Neoplasms - enzymology ; Neoplasms - metabolism ; Oxygen ; protein engineering ; Proteins ; Reactive Oxygen Species - metabolism ; Ribonuclease, Pancreatic - chemistry ; Ribonuclease, Pancreatic - metabolism ; Ribonuclease, Pancreatic - pharmacology ; Ribonuclease, Pancreatic - therapeutic use ; ROS-responsive ; targeted cancer therapy ; Therapy ; Tumors</subject><ispartof>Angewandte Chemie International Edition, 2014-12, Vol.53 (49), p.13444-13448</ispartof><rights>2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim</rights><rights>2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.</rights><rights>2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5474-d4a4b4eacc0573cdb25feb73b76eb066e3a4c64b18f8f276766351eee157abe53</citedby><cites>FETCH-LOGICAL-c5474-d4a4b4eacc0573cdb25feb73b76eb066e3a4c64b18f8f276766351eee157abe53</cites></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.201407234$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fanie.201407234$$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/25287050$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Ming</creatorcontrib><creatorcontrib>Sun, Shuo</creatorcontrib><creatorcontrib>Neufeld, Caleb I.</creatorcontrib><creatorcontrib>Perez-Ramirez, Bernardo</creatorcontrib><creatorcontrib>Xu, Qiaobing</creatorcontrib><title>Reactive Oxygen Species-Responsive Protein Modification and Its Intracellular Delivery for Targeted Cancer Therapy</title><title>Angewandte Chemie International Edition</title><addtitle>Angew. Chem. Int. Ed</addtitle><description>Herein we report a convenient chemical approach to reversibly modulate protein (RNase A) function and develop a protein that is responsive to reactive oxygen species (ROS) for targeted cancer therapy. The conjugation of RNase A with 4‐nitrophenyl 4‐(4,4,5,5‐tetramethyl‐1,3,2‐dioxaborolan‐2‐yl) benzyl carbonate (NBC) blocks protein lysine and temporarily deactivates the protein. However, the treatment of RNase A–NBC with hydrogen peroxide (one major intracellular ROS) efficiently cleaves the NBC conjugation and restores the RNase A activity. Thus, RNase A–NBC can be reactivated inside tumor cells by high levels of intracellular ROS, thereby restoring the cytotoxicity of RNase A for cancer therapy. Due to higher ROS levels inside tumor cells compared to healthy cells, and the resulting different levels of RNase A–NBC reactivation, RNase A–NBC shows a significant specific cytotoxicity against tumor cells.
Reversible protein function modulation was achieved by a convenient chemical approach. RNase A was equipped with a boronic acid group (RNase A–NBC) that responds to reactive oxygen species (ROS). This complex shows cytotoxicity in the presence of ROS, as for example in cancer cells, whereas healthy cells are only affected at significantly higher concentrations.</description><subject>Benzyl Compounds - chemistry</subject><subject>Benzyl Compounds - metabolism</subject><subject>Cancer</subject><subject>Cancer therapies</subject><subject>Carbonates</subject><subject>Carbonates - chemistry</subject><subject>Carbonates - metabolism</subject><subject>Cell Line, Tumor</subject><subject>Conjugation</subject><subject>Cytotoxicity</subject><subject>drug delivery</subject><subject>Enzyme Therapy</subject><subject>Humans</subject><subject>Hydrogen peroxide</subject><subject>Lysine</subject><subject>Modulation</subject><subject>nanoparticles</subject><subject>Neoplasms - drug therapy</subject><subject>Neoplasms - enzymology</subject><subject>Neoplasms - metabolism</subject><subject>Oxygen</subject><subject>protein engineering</subject><subject>Proteins</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Ribonuclease, Pancreatic - chemistry</subject><subject>Ribonuclease, Pancreatic - metabolism</subject><subject>Ribonuclease, Pancreatic - pharmacology</subject><subject>Ribonuclease, Pancreatic - therapeutic use</subject><subject>ROS-responsive</subject><subject>targeted cancer therapy</subject><subject>Therapy</subject><subject>Tumors</subject><issn>1433-7851</issn><issn>1521-3773</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc9v0zAYhiMEYmNw5YgsceGS4t9Oj1M7RqWxsVHgaDnOl-GR2sFOtuW_x6WjQlx2si0_76vPforiNcEzgjF9b7yDGcWEY0UZf1IcEkFJyZRiT_OeM1aqSpCD4kVKN5mvKiyfFwdU0EphgQ-LeAXGDu4W0MX9dA0efenBOkjlFaQ--LS9-RzDAM6jT6FxrbNmcMEj4xu0GhJa-SEaC103diaiJXQ5ESfUhojWJl7DAA1aGG8hn39ANP30snjWmi7Bq4f1qPj64WS9-FieXZyuFsdnpRVc8bLhhtc8T2exUMw2NRUt1IrVSkKNpQRmuJW8JlVbtVRJJSUTBACIUKYGwY6Kd7vePoZfI6RBb1zaTmo8hDFpojDBild4_jgq889VlEmS0bf_oTdhjD4_5A-VVcg5zdRsR9kYUorQ6j66jYmTJlhvxemtOL0XlwNvHmrHegPNHv9rKgPzHXDnOpgeqdPH56uTf8vLXdalAe73WRN_aqmYEvr7-am-_LZcXs6Xa03ZbzCCtGs</recordid><startdate>20141201</startdate><enddate>20141201</enddate><creator>Wang, Ming</creator><creator>Sun, Shuo</creator><creator>Neufeld, Caleb I.</creator><creator>Perez-Ramirez, Bernardo</creator><creator>Xu, Qiaobing</creator><general>WILEY-VCH Verlag</general><general>WILEY‐VCH Verlag</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</scope><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><scope>7X8</scope><scope>7SR</scope><scope>8BQ</scope><scope>8FD</scope><scope>JG9</scope></search><sort><creationdate>20141201</creationdate><title>Reactive Oxygen Species-Responsive Protein Modification and Its Intracellular Delivery for Targeted Cancer Therapy</title><author>Wang, Ming ; Sun, Shuo ; Neufeld, Caleb I. ; Perez-Ramirez, Bernardo ; Xu, Qiaobing</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5474-d4a4b4eacc0573cdb25feb73b76eb066e3a4c64b18f8f276766351eee157abe53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Benzyl Compounds - chemistry</topic><topic>Benzyl Compounds - metabolism</topic><topic>Cancer</topic><topic>Cancer therapies</topic><topic>Carbonates</topic><topic>Carbonates - chemistry</topic><topic>Carbonates - metabolism</topic><topic>Cell Line, Tumor</topic><topic>Conjugation</topic><topic>Cytotoxicity</topic><topic>drug delivery</topic><topic>Enzyme Therapy</topic><topic>Humans</topic><topic>Hydrogen peroxide</topic><topic>Lysine</topic><topic>Modulation</topic><topic>nanoparticles</topic><topic>Neoplasms - drug therapy</topic><topic>Neoplasms - enzymology</topic><topic>Neoplasms - metabolism</topic><topic>Oxygen</topic><topic>protein engineering</topic><topic>Proteins</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Ribonuclease, Pancreatic - chemistry</topic><topic>Ribonuclease, Pancreatic - metabolism</topic><topic>Ribonuclease, Pancreatic - pharmacology</topic><topic>Ribonuclease, Pancreatic - therapeutic use</topic><topic>ROS-responsive</topic><topic>targeted cancer therapy</topic><topic>Therapy</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Ming</creatorcontrib><creatorcontrib>Sun, Shuo</creatorcontrib><creatorcontrib>Neufeld, Caleb I.</creatorcontrib><creatorcontrib>Perez-Ramirez, Bernardo</creatorcontrib><creatorcontrib>Xu, Qiaobing</creatorcontrib><collection>Istex</collection><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><collection>MEDLINE - Academic</collection><collection>Engineered Materials Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Materials Research Database</collection><jtitle>Angewandte Chemie International Edition</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Ming</au><au>Sun, Shuo</au><au>Neufeld, Caleb I.</au><au>Perez-Ramirez, Bernardo</au><au>Xu, Qiaobing</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Reactive Oxygen Species-Responsive Protein Modification and Its Intracellular Delivery for Targeted Cancer Therapy</atitle><jtitle>Angewandte Chemie International Edition</jtitle><addtitle>Angew. Chem. Int. Ed</addtitle><date>2014-12-01</date><risdate>2014</risdate><volume>53</volume><issue>49</issue><spage>13444</spage><epage>13448</epage><pages>13444-13448</pages><issn>1433-7851</issn><eissn>1521-3773</eissn><coden>ACIEAY</coden><abstract>Herein we report a convenient chemical approach to reversibly modulate protein (RNase A) function and develop a protein that is responsive to reactive oxygen species (ROS) for targeted cancer therapy. The conjugation of RNase A with 4‐nitrophenyl 4‐(4,4,5,5‐tetramethyl‐1,3,2‐dioxaborolan‐2‐yl) benzyl carbonate (NBC) blocks protein lysine and temporarily deactivates the protein. However, the treatment of RNase A–NBC with hydrogen peroxide (one major intracellular ROS) efficiently cleaves the NBC conjugation and restores the RNase A activity. Thus, RNase A–NBC can be reactivated inside tumor cells by high levels of intracellular ROS, thereby restoring the cytotoxicity of RNase A for cancer therapy. Due to higher ROS levels inside tumor cells compared to healthy cells, and the resulting different levels of RNase A–NBC reactivation, RNase A–NBC shows a significant specific cytotoxicity against tumor cells.
Reversible protein function modulation was achieved by a convenient chemical approach. RNase A was equipped with a boronic acid group (RNase A–NBC) that responds to reactive oxygen species (ROS). This complex shows cytotoxicity in the presence of ROS, as for example in cancer cells, whereas healthy cells are only affected at significantly higher concentrations.</abstract><cop>Weinheim</cop><pub>WILEY-VCH Verlag</pub><pmid>25287050</pmid><doi>10.1002/anie.201407234</doi><tpages>5</tpages><edition>International ed. in English</edition></addata></record> |
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| subjects | Benzyl Compounds - chemistry Benzyl Compounds - metabolism Cancer Cancer therapies Carbonates Carbonates - chemistry Carbonates - metabolism Cell Line, Tumor Conjugation Cytotoxicity drug delivery Enzyme Therapy Humans Hydrogen peroxide Lysine Modulation nanoparticles Neoplasms - drug therapy Neoplasms - enzymology Neoplasms - metabolism Oxygen protein engineering Proteins Reactive Oxygen Species - metabolism Ribonuclease, Pancreatic - chemistry Ribonuclease, Pancreatic - metabolism Ribonuclease, Pancreatic - pharmacology Ribonuclease, Pancreatic - therapeutic use ROS-responsive targeted cancer therapy Therapy Tumors |
| title | Reactive Oxygen Species-Responsive Protein Modification and Its Intracellular Delivery for Targeted Cancer Therapy |
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