Oncolytic Nanoreactors Producing Hydrogen Peroxide for Oxidative Cancer Therapy
In situ generation of anticancer agents at the place of the disease is a new paradigm for cancer therapy. The production of highly potent drugs by nanoreactors through a facile synthesis pathway is demanded. We report an oncolytic nanoreactor platform loaded with the enzyme glucose oxidase (GOX) to...
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Veröffentlicht in: | Nano letters 2020-01, Vol.20 (1), p.526-533 |
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creator | Jo, Seong-Min Wurm, Frederik R Landfester, Katharina |
description | In situ generation of anticancer agents at the place of the disease is a new paradigm for cancer therapy. The production of highly potent drugs by nanoreactors through a facile synthesis pathway is demanded. We report an oncolytic nanoreactor platform loaded with the enzyme glucose oxidase (GOX) to produce hydrogen peroxide. For the first time, we realized a core–shell structure with encapsulated GOX under mild synthetic conditions, which ensured high remaining activity of GOX inside of the nanoreactor. Moreover, the nanoreactor protected the loaded GOX from proteolysis and contributed to increased thermal stability of the enzyme. The nanoreactors were effectively taken up into different cancer cells, in which they produced hydrogen peroxide by consuming intracellular glucose and oxygen, thereby leading to effective death of the cancer cells. In summary, our robust nanoreactors are a promising platform for effective anticancer therapy and sustained enzyme utilization. |
doi_str_mv | 10.1021/acs.nanolett.9b04263 |
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The production of highly potent drugs by nanoreactors through a facile synthesis pathway is demanded. We report an oncolytic nanoreactor platform loaded with the enzyme glucose oxidase (GOX) to produce hydrogen peroxide. For the first time, we realized a core–shell structure with encapsulated GOX under mild synthetic conditions, which ensured high remaining activity of GOX inside of the nanoreactor. Moreover, the nanoreactor protected the loaded GOX from proteolysis and contributed to increased thermal stability of the enzyme. The nanoreactors were effectively taken up into different cancer cells, in which they produced hydrogen peroxide by consuming intracellular glucose and oxygen, thereby leading to effective death of the cancer cells. In summary, our robust nanoreactors are a promising platform for effective anticancer therapy and sustained enzyme utilization.</description><subject>Antineoplastic Agents - pharmacokinetics</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Caco-2 Cells</subject><subject>Glucose Oxidase - chemistry</subject><subject>Glucose Oxidase - pharmacokinetics</subject><subject>Glucose Oxidase - pharmacology</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Hydrogen Peroxide - pharmacokinetics</subject><subject>Hydrogen Peroxide - pharmacology</subject><subject>MCF-7 Cells</subject><subject>Neoplasms - drug therapy</subject><subject>Neoplasms - metabolism</subject><subject>Neoplasms - pathology</subject><subject>Oxidation-Reduction - drug effects</subject><issn>1530-6984</issn><issn>1530-6992</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMtOwzAQRS0EoqXwBwj5B1LGj7jOElVAkSrSRVlHjj0pqVq7clJE_p5UfSxZzV3cc6U5hDwyGDPg7NnYZuyNDxts23FWguRKXJEhSwUkKsv49SVrOSB3TbMGgEykcEsGgk10lnI1JHnubdh0bW3pZz8W0dg2xIYuYnB7W_sVnXUuhhV6usAYfmuHtAqR5n0ybf2DdGq8xUiX3xjNrrsnN5XZNPhwuiPy9fa6nM6Sef7-MX2ZJ0YqaBMmUyNRO2UVrzJdaVeKsiqFsFKDknqinQExqTh3CBxLWyqnTMYYpsZZUGJE5HHXxtA0EatiF-utiV3BoDj4KXo_xdlPcfLTY09HbLcvt-gu0FlIX4Bj4YCvwz76_ov_N_8AJLt3BQ</recordid><startdate>20200108</startdate><enddate>20200108</enddate><creator>Jo, Seong-Min</creator><creator>Wurm, Frederik R</creator><creator>Landfester, Katharina</creator><general>American Chemical Society</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><orcidid>https://orcid.org/0000-0001-9591-4638</orcidid><orcidid>https://orcid.org/0000-0002-6955-8489</orcidid></search><sort><creationdate>20200108</creationdate><title>Oncolytic Nanoreactors Producing Hydrogen Peroxide for Oxidative Cancer Therapy</title><author>Jo, Seong-Min ; Wurm, Frederik R ; Landfester, Katharina</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a460t-145a4e8d6c62f98f8db3bfb33c48064878da037f22de02ebcb6d6a911e5adc063</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Antineoplastic Agents - pharmacokinetics</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Caco-2 Cells</topic><topic>Glucose Oxidase - chemistry</topic><topic>Glucose Oxidase - pharmacokinetics</topic><topic>Glucose Oxidase - pharmacology</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>Hydrogen Peroxide - pharmacokinetics</topic><topic>Hydrogen Peroxide - pharmacology</topic><topic>MCF-7 Cells</topic><topic>Neoplasms - drug therapy</topic><topic>Neoplasms - metabolism</topic><topic>Neoplasms - pathology</topic><topic>Oxidation-Reduction - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jo, Seong-Min</creatorcontrib><creatorcontrib>Wurm, Frederik R</creatorcontrib><creatorcontrib>Landfester, Katharina</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Nano letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jo, Seong-Min</au><au>Wurm, Frederik R</au><au>Landfester, Katharina</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Oncolytic Nanoreactors Producing Hydrogen Peroxide for Oxidative Cancer Therapy</atitle><jtitle>Nano letters</jtitle><addtitle>Nano Lett</addtitle><date>2020-01-08</date><risdate>2020</risdate><volume>20</volume><issue>1</issue><spage>526</spage><epage>533</epage><pages>526-533</pages><issn>1530-6984</issn><eissn>1530-6992</eissn><abstract>In situ generation of anticancer agents at the place of the disease is a new paradigm for cancer therapy. The production of highly potent drugs by nanoreactors through a facile synthesis pathway is demanded. We report an oncolytic nanoreactor platform loaded with the enzyme glucose oxidase (GOX) to produce hydrogen peroxide. For the first time, we realized a core–shell structure with encapsulated GOX under mild synthetic conditions, which ensured high remaining activity of GOX inside of the nanoreactor. Moreover, the nanoreactor protected the loaded GOX from proteolysis and contributed to increased thermal stability of the enzyme. The nanoreactors were effectively taken up into different cancer cells, in which they produced hydrogen peroxide by consuming intracellular glucose and oxygen, thereby leading to effective death of the cancer cells. 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subjects | Antineoplastic Agents - pharmacokinetics Antineoplastic Agents - pharmacology Caco-2 Cells Glucose Oxidase - chemistry Glucose Oxidase - pharmacokinetics Glucose Oxidase - pharmacology HeLa Cells Humans Hydrogen Peroxide - pharmacokinetics Hydrogen Peroxide - pharmacology MCF-7 Cells Neoplasms - drug therapy Neoplasms - metabolism Neoplasms - pathology Oxidation-Reduction - drug effects |
title | Oncolytic Nanoreactors Producing Hydrogen Peroxide for Oxidative Cancer Therapy |
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