Actively targeted delivery of anticancer drug to tumor cells by redox-responsive star-shaped micelles
Abstract In cancer therapy nanocargos based on star-shaped polymer exhibit unique features such as better stability, smaller size distribution and higher drug capacity in comparison to linear polymeric micelles. In this study, we developed a multifunctional star-shaped micellar system by combination...
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| Veröffentlicht in: | Biomaterials 2014-10, Vol.35 (30), p.8711-8722 |
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| creator | Shi, Chunli Guo, Xing Qu, Qianqian Tang, Zhaomin Wang, Yi Zhou, Shaobing |
| description | Abstract In cancer therapy nanocargos based on star-shaped polymer exhibit unique features such as better stability, smaller size distribution and higher drug capacity in comparison to linear polymeric micelles. In this study, we developed a multifunctional star-shaped micellar system by combination of active targeting ability and redox-responsive behavior. The star-shaped micelles with good stability were self-assembled from four-arm poly(ε-caprolactone)-poly(ethylene glycol) copolymer. The redox-responsive behaviors of these micelles triggered by glutathione were evaluated from the changes of micellar size, morphology and molecular weight. In vitro drug release profiles exhibited that in a stimulated normal physiological environment, the redox-responsive star-shaped micelles could maintain good stability, whereas in a reducing and acid environment similar with that of tumor cells, the encapsulated agent was promptly released. In vitro cellular uptake and subcellular localization of these micelles were further studied with confocal laser scanning microscopy and flow cytometry against the human cervical cancer cell line HeLa. In vivo and ex vivo DOX fluorescence imaging displayed that these FA-functionalized star-shaped micelles possessed much better specificity to target solid tumor. Both the qualitative and quantitative results of the antitumor effect in 4T1 tumor-bearing BALB/c mice demonstrated that these redox-responsive star-shaped micelles have a high therapeutic efficiency to artificial solid tumor. Therefore, the multifunctional star-shaped micelles are a potential platform for targeted anticancer drug delivery. |
| doi_str_mv | 10.1016/j.biomaterials.2014.06.036 |
| format | Article |
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In this study, we developed a multifunctional star-shaped micellar system by combination of active targeting ability and redox-responsive behavior. The star-shaped micelles with good stability were self-assembled from four-arm poly(ε-caprolactone)-poly(ethylene glycol) copolymer. The redox-responsive behaviors of these micelles triggered by glutathione were evaluated from the changes of micellar size, morphology and molecular weight. In vitro drug release profiles exhibited that in a stimulated normal physiological environment, the redox-responsive star-shaped micelles could maintain good stability, whereas in a reducing and acid environment similar with that of tumor cells, the encapsulated agent was promptly released. In vitro cellular uptake and subcellular localization of these micelles were further studied with confocal laser scanning microscopy and flow cytometry against the human cervical cancer cell line HeLa. In vivo and ex vivo DOX fluorescence imaging displayed that these FA-functionalized star-shaped micelles possessed much better specificity to target solid tumor. Both the qualitative and quantitative results of the antitumor effect in 4T1 tumor-bearing BALB/c mice demonstrated that these redox-responsive star-shaped micelles have a high therapeutic efficiency to artificial solid tumor. Therefore, the multifunctional star-shaped micelles are a potential platform for targeted anticancer drug delivery.</description><identifier>ISSN: 0142-9612</identifier><identifier>EISSN: 1878-5905</identifier><identifier>DOI: 10.1016/j.biomaterials.2014.06.036</identifier><identifier>PMID: 25002267</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Advanced Basic Science ; Animals ; Antineoplastic Agents - administration & dosage ; Antineoplastic Agents - pharmacology ; Antineoplastic Agents - therapeutic use ; Biomedical materials ; Cancer ; Cell Death - drug effects ; Cell Line, Tumor ; Dentistry ; Doxorubicin - pharmacology ; Doxorubicin - therapeutic use ; Drug delivery ; Drug delivery systems ; Drug Delivery Systems - methods ; Drugs ; Female ; Flow Cytometry ; Folic Acid - chemistry ; Glutathione - pharmacology ; Humans ; In Situ Nick-End Labeling ; In vitro testing ; Mice, Inbred BALB C ; Mice, Nude ; Micelles ; Nanocarrier ; Neoplasms - drug therapy ; Neoplasms - pathology ; Oxidation-Reduction - drug effects ; Particle Size ; Polyesters - chemical synthesis ; Polyesters - chemistry ; Proton Magnetic Resonance Spectroscopy ; Redox-responsive ; Stability ; Star-shaped ; Tissue Distribution - drug effects ; Tumor targeting ; Tumors</subject><ispartof>Biomaterials, 2014-10, Vol.35 (30), p.8711-8722</ispartof><rights>Elsevier Ltd</rights><rights>2014 Elsevier Ltd</rights><rights>Copyright © 2014 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c501t-9160b6b7a26cc6631fe41a27e6aefb3da85553366060d8a78498abbf819d10ec3</citedby><cites>FETCH-LOGICAL-c501t-9160b6b7a26cc6631fe41a27e6aefb3da85553366060d8a78498abbf819d10ec3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0142961214007273$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25002267$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shi, Chunli</creatorcontrib><creatorcontrib>Guo, Xing</creatorcontrib><creatorcontrib>Qu, Qianqian</creatorcontrib><creatorcontrib>Tang, Zhaomin</creatorcontrib><creatorcontrib>Wang, Yi</creatorcontrib><creatorcontrib>Zhou, Shaobing</creatorcontrib><title>Actively targeted delivery of anticancer drug to tumor cells by redox-responsive star-shaped micelles</title><title>Biomaterials</title><addtitle>Biomaterials</addtitle><description>Abstract In cancer therapy nanocargos based on star-shaped polymer exhibit unique features such as better stability, smaller size distribution and higher drug capacity in comparison to linear polymeric micelles. In this study, we developed a multifunctional star-shaped micellar system by combination of active targeting ability and redox-responsive behavior. The star-shaped micelles with good stability were self-assembled from four-arm poly(ε-caprolactone)-poly(ethylene glycol) copolymer. The redox-responsive behaviors of these micelles triggered by glutathione were evaluated from the changes of micellar size, morphology and molecular weight. In vitro drug release profiles exhibited that in a stimulated normal physiological environment, the redox-responsive star-shaped micelles could maintain good stability, whereas in a reducing and acid environment similar with that of tumor cells, the encapsulated agent was promptly released. In vitro cellular uptake and subcellular localization of these micelles were further studied with confocal laser scanning microscopy and flow cytometry against the human cervical cancer cell line HeLa. In vivo and ex vivo DOX fluorescence imaging displayed that these FA-functionalized star-shaped micelles possessed much better specificity to target solid tumor. Both the qualitative and quantitative results of the antitumor effect in 4T1 tumor-bearing BALB/c mice demonstrated that these redox-responsive star-shaped micelles have a high therapeutic efficiency to artificial solid tumor. Therefore, the multifunctional star-shaped micelles are a potential platform for targeted anticancer drug delivery.</description><subject>Advanced Basic Science</subject><subject>Animals</subject><subject>Antineoplastic Agents - administration & dosage</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Biomedical materials</subject><subject>Cancer</subject><subject>Cell Death - drug effects</subject><subject>Cell Line, Tumor</subject><subject>Dentistry</subject><subject>Doxorubicin - pharmacology</subject><subject>Doxorubicin - therapeutic use</subject><subject>Drug delivery</subject><subject>Drug delivery systems</subject><subject>Drug Delivery Systems - methods</subject><subject>Drugs</subject><subject>Female</subject><subject>Flow Cytometry</subject><subject>Folic Acid - chemistry</subject><subject>Glutathione - pharmacology</subject><subject>Humans</subject><subject>In Situ Nick-End Labeling</subject><subject>In vitro testing</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>Micelles</subject><subject>Nanocarrier</subject><subject>Neoplasms - drug therapy</subject><subject>Neoplasms - pathology</subject><subject>Oxidation-Reduction - drug effects</subject><subject>Particle Size</subject><subject>Polyesters - chemical synthesis</subject><subject>Polyesters - chemistry</subject><subject>Proton Magnetic Resonance Spectroscopy</subject><subject>Redox-responsive</subject><subject>Stability</subject><subject>Star-shaped</subject><subject>Tissue Distribution - drug effects</subject><subject>Tumor targeting</subject><subject>Tumors</subject><issn>0142-9612</issn><issn>1878-5905</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNks1u1TAQhS0EopfCKyCLFZuEsRM7CQukqvxVqtRFYW059qT4ksQX26mat8fRLQixaVeW7XPOjOYbQt4wKBkw-W5f9s5POmFweowlB1aXIEuo5BOyY23TFqID8ZTs8gcvOsn4CXkR4x7yHWr-nJxwAcC5bHYEz0xytziuNOlwgwkttTjml7BSP1A9J2f0bDBQG5YbmjxNy-QDNTiOkfYrDWj9XREwHvwcs4_GHFTEH_qQoya36TC-JM-G3Cq-uj9PyffPn76dfy0ur75cnJ9dFkYAS0XHJPSybzSXxkhZsQFrpnmDUuPQV1a3QoiqkhIk2FY3bd21uu-HlnWWAZrqlLw95h6C_7VgTGpycWtBz-iXqJisOe8Ek-wRUt7k0YGQD0tF3crcVrOlvj9KTfAxBhzUIbhJh1UxUBs8tVf_wlMbPAVSZXjZ_Pq-ztJPaP9a_9DKgo9HAeYZ3joMKhqHmY51AU1S1rvH1fnwX4wZ3Zw5jz9xxbj3S5g3D1ORK1DX2xptW5S3BxreVNVvwsPHPw</recordid><startdate>20141001</startdate><enddate>20141001</enddate><creator>Shi, Chunli</creator><creator>Guo, Xing</creator><creator>Qu, Qianqian</creator><creator>Tang, Zhaomin</creator><creator>Wang, Yi</creator><creator>Zhou, Shaobing</creator><general>Elsevier Ltd</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>7X8</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7SR</scope><scope>7TB</scope><scope>7U5</scope><scope>8BQ</scope><scope>F28</scope><scope>JG9</scope><scope>L7M</scope></search><sort><creationdate>20141001</creationdate><title>Actively targeted delivery of anticancer drug to tumor cells by redox-responsive star-shaped micelles</title><author>Shi, Chunli ; Guo, Xing ; Qu, Qianqian ; Tang, Zhaomin ; Wang, Yi ; Zhou, Shaobing</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c501t-9160b6b7a26cc6631fe41a27e6aefb3da85553366060d8a78498abbf819d10ec3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Advanced Basic Science</topic><topic>Animals</topic><topic>Antineoplastic Agents - administration & dosage</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>Biomedical materials</topic><topic>Cancer</topic><topic>Cell Death - drug effects</topic><topic>Cell Line, Tumor</topic><topic>Dentistry</topic><topic>Doxorubicin - pharmacology</topic><topic>Doxorubicin - therapeutic use</topic><topic>Drug delivery</topic><topic>Drug delivery systems</topic><topic>Drug Delivery Systems - methods</topic><topic>Drugs</topic><topic>Female</topic><topic>Flow Cytometry</topic><topic>Folic Acid - chemistry</topic><topic>Glutathione - pharmacology</topic><topic>Humans</topic><topic>In Situ Nick-End Labeling</topic><topic>In vitro testing</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Nude</topic><topic>Micelles</topic><topic>Nanocarrier</topic><topic>Neoplasms - drug therapy</topic><topic>Neoplasms - pathology</topic><topic>Oxidation-Reduction - drug effects</topic><topic>Particle Size</topic><topic>Polyesters - chemical synthesis</topic><topic>Polyesters - chemistry</topic><topic>Proton Magnetic Resonance Spectroscopy</topic><topic>Redox-responsive</topic><topic>Stability</topic><topic>Star-shaped</topic><topic>Tissue Distribution - drug effects</topic><topic>Tumor targeting</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shi, Chunli</creatorcontrib><creatorcontrib>Guo, Xing</creatorcontrib><creatorcontrib>Qu, Qianqian</creatorcontrib><creatorcontrib>Tang, Zhaomin</creatorcontrib><creatorcontrib>Wang, Yi</creatorcontrib><creatorcontrib>Zhou, Shaobing</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Materials Research Database</collection><collection>Advanced Technologies Database with Aerospace</collection><jtitle>Biomaterials</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shi, Chunli</au><au>Guo, Xing</au><au>Qu, Qianqian</au><au>Tang, Zhaomin</au><au>Wang, Yi</au><au>Zhou, Shaobing</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Actively targeted delivery of anticancer drug to tumor cells by redox-responsive star-shaped micelles</atitle><jtitle>Biomaterials</jtitle><addtitle>Biomaterials</addtitle><date>2014-10-01</date><risdate>2014</risdate><volume>35</volume><issue>30</issue><spage>8711</spage><epage>8722</epage><pages>8711-8722</pages><issn>0142-9612</issn><eissn>1878-5905</eissn><abstract>Abstract In cancer therapy nanocargos based on star-shaped polymer exhibit unique features such as better stability, smaller size distribution and higher drug capacity in comparison to linear polymeric micelles. In this study, we developed a multifunctional star-shaped micellar system by combination of active targeting ability and redox-responsive behavior. The star-shaped micelles with good stability were self-assembled from four-arm poly(ε-caprolactone)-poly(ethylene glycol) copolymer. The redox-responsive behaviors of these micelles triggered by glutathione were evaluated from the changes of micellar size, morphology and molecular weight. In vitro drug release profiles exhibited that in a stimulated normal physiological environment, the redox-responsive star-shaped micelles could maintain good stability, whereas in a reducing and acid environment similar with that of tumor cells, the encapsulated agent was promptly released. In vitro cellular uptake and subcellular localization of these micelles were further studied with confocal laser scanning microscopy and flow cytometry against the human cervical cancer cell line HeLa. In vivo and ex vivo DOX fluorescence imaging displayed that these FA-functionalized star-shaped micelles possessed much better specificity to target solid tumor. Both the qualitative and quantitative results of the antitumor effect in 4T1 tumor-bearing BALB/c mice demonstrated that these redox-responsive star-shaped micelles have a high therapeutic efficiency to artificial solid tumor. Therefore, the multifunctional star-shaped micelles are a potential platform for targeted anticancer drug delivery.</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>25002267</pmid><doi>10.1016/j.biomaterials.2014.06.036</doi><tpages>12</tpages></addata></record> |
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| ispartof | Biomaterials, 2014-10, Vol.35 (30), p.8711-8722 |
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| subjects | Advanced Basic Science Animals Antineoplastic Agents - administration & dosage Antineoplastic Agents - pharmacology Antineoplastic Agents - therapeutic use Biomedical materials Cancer Cell Death - drug effects Cell Line, Tumor Dentistry Doxorubicin - pharmacology Doxorubicin - therapeutic use Drug delivery Drug delivery systems Drug Delivery Systems - methods Drugs Female Flow Cytometry Folic Acid - chemistry Glutathione - pharmacology Humans In Situ Nick-End Labeling In vitro testing Mice, Inbred BALB C Mice, Nude Micelles Nanocarrier Neoplasms - drug therapy Neoplasms - pathology Oxidation-Reduction - drug effects Particle Size Polyesters - chemical synthesis Polyesters - chemistry Proton Magnetic Resonance Spectroscopy Redox-responsive Stability Star-shaped Tissue Distribution - drug effects Tumor targeting Tumors |
| title | Actively targeted delivery of anticancer drug to tumor cells by redox-responsive star-shaped micelles |
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