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Glutathione-Triggered “Off–On” Release of Anticancer Drugs from Dendrimer-Encapsulated Gold Nanoparticles
Polymeric nanoparticles that can stably load anticancer drugs and release them in response to a specific trigger such as glutathione are of great interest in cancer therapy. In the present study, dendrimer-encapsulated gold nanoparticles (DEGNPs) were synthesized and used as carriers of thiolated an...
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Published in: | Journal of the American Chemical Society 2013-07, Vol.135 (26), p.9805-9810 |
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container_end_page | 9810 |
container_issue | 26 |
container_start_page | 9805 |
container_title | Journal of the American Chemical Society |
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creator | Wang, Xinyu Cai, Xiaopan Hu, Jingjing Shao, Naimin Wang, Fei Zhang, Qiang Xiao, Jianru Cheng, Yiyun |
description | Polymeric nanoparticles that can stably load anticancer drugs and release them in response to a specific trigger such as glutathione are of great interest in cancer therapy. In the present study, dendrimer-encapsulated gold nanoparticles (DEGNPs) were synthesized and used as carriers of thiolated anticancer drugs. Thiol-containing drugs such as captopril and 6-mercaptopurine loaded within DEGNPs showed an “Off–On” release behavior in the presence of thiol-reducing agents such as glutathione and dithiothreitol. Thiolated doxorubicin and cisplatin, loaded within the nanoparticle, showed much reduced cytotoxicity as compared to the free anticancer compounds. The toxicity of drug-loaded DEGNPs can be enhanced by improving the intracellular glutathione. Glutathione-triggered release of thiolated doxorubicin within cancer cells is further confirmed by flow cytometry and confocal laser scan microscopy studies. In addition, DEGNPs showed excellent biocompatibility on several cell lines. This study provides a new insight into biomedical applications of dendrimers and dendrimer-encapsulated nanoparticles. |
doi_str_mv | 10.1021/ja402903h |
format | article |
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In the present study, dendrimer-encapsulated gold nanoparticles (DEGNPs) were synthesized and used as carriers of thiolated anticancer drugs. Thiol-containing drugs such as captopril and 6-mercaptopurine loaded within DEGNPs showed an “Off–On” release behavior in the presence of thiol-reducing agents such as glutathione and dithiothreitol. Thiolated doxorubicin and cisplatin, loaded within the nanoparticle, showed much reduced cytotoxicity as compared to the free anticancer compounds. The toxicity of drug-loaded DEGNPs can be enhanced by improving the intracellular glutathione. Glutathione-triggered release of thiolated doxorubicin within cancer cells is further confirmed by flow cytometry and confocal laser scan microscopy studies. In addition, DEGNPs showed excellent biocompatibility on several cell lines. 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Am. Chem. Soc</addtitle><description>Polymeric nanoparticles that can stably load anticancer drugs and release them in response to a specific trigger such as glutathione are of great interest in cancer therapy. In the present study, dendrimer-encapsulated gold nanoparticles (DEGNPs) were synthesized and used as carriers of thiolated anticancer drugs. Thiol-containing drugs such as captopril and 6-mercaptopurine loaded within DEGNPs showed an “Off–On” release behavior in the presence of thiol-reducing agents such as glutathione and dithiothreitol. Thiolated doxorubicin and cisplatin, loaded within the nanoparticle, showed much reduced cytotoxicity as compared to the free anticancer compounds. The toxicity of drug-loaded DEGNPs can be enhanced by improving the intracellular glutathione. Glutathione-triggered release of thiolated doxorubicin within cancer cells is further confirmed by flow cytometry and confocal laser scan microscopy studies. In addition, DEGNPs showed excellent biocompatibility on several cell lines. This study provides a new insight into biomedical applications of dendrimers and dendrimer-encapsulated nanoparticles.</description><subject>Antineoplastic Agents - chemistry</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Cell Survival - drug effects</subject><subject>Dendrimers - chemistry</subject><subject>Dose-Response Relationship, Drug</subject><subject>Doxorubicin - chemistry</subject><subject>Doxorubicin - pharmacology</subject><subject>Drug Carriers - chemistry</subject><subject>Drug Screening Assays, Antitumor</subject><subject>Glutathione - chemistry</subject><subject>Gold - chemistry</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Metal Nanoparticles - chemistry</subject><subject>Molecular Structure</subject><subject>Structure-Activity Relationship</subject><subject>Sulfhydryl Compounds - chemistry</subject><issn>0002-7863</issn><issn>1520-5126</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><recordid>eNpt0L9OwzAQBnALgWgpDLwAysLAEDg7cf6MVVsKUkUlVObo4pzbVGlS2cnA1ndghZfrk2BU6MR0Oul3n04fY9cc7jkI_rDGEEQKweqE9bkU4EsuolPWBwDhx0kU9NiFtWu3hiLh56wngjhJYx70WTOtuhbbVdnU5C9MuVySocLb7z7nWu93H_N6v_vyXqkitOQ12hvWbamwVmS8semW1tOm2XhjqgtTbsj4k1rh1nYVti5m2lSF94J1s0Xjziqyl-xMY2Xp6ncO2NvjZDF68mfz6fNoOPMx4LL1ZSw0yTSEAlWeE0YgRVjIRElASbwoEGKRxJGkOM1BpYAxOa0FSOlUFAzY3SFXmcZaQzrbuv_QvGccsp_SsmNpzt4c7LbLN1Qc5V9LDtweACqbrZvO1O71f4K-ASKpdus</recordid><startdate>20130703</startdate><enddate>20130703</enddate><creator>Wang, Xinyu</creator><creator>Cai, Xiaopan</creator><creator>Hu, Jingjing</creator><creator>Shao, Naimin</creator><creator>Wang, Fei</creator><creator>Zhang, Qiang</creator><creator>Xiao, Jianru</creator><creator>Cheng, Yiyun</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></search><sort><creationdate>20130703</creationdate><title>Glutathione-Triggered “Off–On” Release of Anticancer Drugs from Dendrimer-Encapsulated Gold Nanoparticles</title><author>Wang, Xinyu ; Cai, Xiaopan ; Hu, Jingjing ; Shao, Naimin ; Wang, Fei ; Zhang, Qiang ; Xiao, Jianru ; Cheng, Yiyun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a315t-572fe5940dacbbea60524d58c50a5e1dda0728765e79b0c90a7e940f205558c63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Antineoplastic Agents - chemistry</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Cell Survival - drug effects</topic><topic>Dendrimers - chemistry</topic><topic>Dose-Response Relationship, Drug</topic><topic>Doxorubicin - chemistry</topic><topic>Doxorubicin - pharmacology</topic><topic>Drug Carriers - chemistry</topic><topic>Drug Screening Assays, Antitumor</topic><topic>Glutathione - chemistry</topic><topic>Gold - chemistry</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>Metal Nanoparticles - chemistry</topic><topic>Molecular Structure</topic><topic>Structure-Activity Relationship</topic><topic>Sulfhydryl Compounds - chemistry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Xinyu</creatorcontrib><creatorcontrib>Cai, Xiaopan</creatorcontrib><creatorcontrib>Hu, Jingjing</creatorcontrib><creatorcontrib>Shao, Naimin</creatorcontrib><creatorcontrib>Wang, Fei</creatorcontrib><creatorcontrib>Zhang, Qiang</creatorcontrib><creatorcontrib>Xiao, Jianru</creatorcontrib><creatorcontrib>Cheng, Yiyun</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Journal of the American Chemical Society</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Xinyu</au><au>Cai, Xiaopan</au><au>Hu, Jingjing</au><au>Shao, Naimin</au><au>Wang, Fei</au><au>Zhang, Qiang</au><au>Xiao, Jianru</au><au>Cheng, Yiyun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Glutathione-Triggered “Off–On” Release of Anticancer Drugs from Dendrimer-Encapsulated Gold Nanoparticles</atitle><jtitle>Journal of the American Chemical Society</jtitle><addtitle>J. Am. Chem. Soc</addtitle><date>2013-07-03</date><risdate>2013</risdate><volume>135</volume><issue>26</issue><spage>9805</spage><epage>9810</epage><pages>9805-9810</pages><issn>0002-7863</issn><eissn>1520-5126</eissn><abstract>Polymeric nanoparticles that can stably load anticancer drugs and release them in response to a specific trigger such as glutathione are of great interest in cancer therapy. In the present study, dendrimer-encapsulated gold nanoparticles (DEGNPs) were synthesized and used as carriers of thiolated anticancer drugs. Thiol-containing drugs such as captopril and 6-mercaptopurine loaded within DEGNPs showed an “Off–On” release behavior in the presence of thiol-reducing agents such as glutathione and dithiothreitol. Thiolated doxorubicin and cisplatin, loaded within the nanoparticle, showed much reduced cytotoxicity as compared to the free anticancer compounds. The toxicity of drug-loaded DEGNPs can be enhanced by improving the intracellular glutathione. Glutathione-triggered release of thiolated doxorubicin within cancer cells is further confirmed by flow cytometry and confocal laser scan microscopy studies. In addition, DEGNPs showed excellent biocompatibility on several cell lines. This study provides a new insight into biomedical applications of dendrimers and dendrimer-encapsulated nanoparticles.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>23789713</pmid><doi>10.1021/ja402903h</doi><tpages>6</tpages></addata></record> |
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subjects | Antineoplastic Agents - chemistry Antineoplastic Agents - pharmacology Cell Survival - drug effects Dendrimers - chemistry Dose-Response Relationship, Drug Doxorubicin - chemistry Doxorubicin - pharmacology Drug Carriers - chemistry Drug Screening Assays, Antitumor Glutathione - chemistry Gold - chemistry HeLa Cells Humans Metal Nanoparticles - chemistry Molecular Structure Structure-Activity Relationship Sulfhydryl Compounds - chemistry |
title | Glutathione-Triggered “Off–On” Release of Anticancer Drugs from Dendrimer-Encapsulated Gold Nanoparticles |
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