Thermally Controlled Release of Anticancer Drug from Self-Assembled γ-Substituted Amphiphilic Poly(ε-caprolactone) Micellar Nanoparticles
A thermo-responsive poly{γ-2-[2-(2-methoxyethoxy)ethoxy]ethoxy-ε-caprolactone}-b-poly(γ-octyloxy-ε-caprolactone) (PMEEECL- b -POCTCL) diblock copolymer was synthesized by ring-opening polymerization using tin octanoate (Sn(Oct)2) catalyst and a fluorescent dansyl initiator. The PMEEECL- b -POCTCL ha...
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| Veröffentlicht in: | Biomacromolecules 2012-07, Vol.13 (7), p.2163-2173 |
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| creator | Cheng, Yixing Hao, Jing Lee, L. Andrew Biewer, Michael C Wang, Qian Stefan, Mihaela C |
| description | A thermo-responsive poly{γ-2-[2-(2-methoxyethoxy)ethoxy]ethoxy-ε-caprolactone}-b-poly(γ-octyloxy-ε-caprolactone) (PMEEECL- b -POCTCL) diblock copolymer was synthesized by ring-opening polymerization using tin octanoate (Sn(Oct)2) catalyst and a fluorescent dansyl initiator. The PMEEECL- b -POCTCL had a lower critical solution temperature (LCST) of 38 °C, and it was employed to prepare thermally responsive micelles. Nile Red and Doxorubicin (DOX) were loaded into the micelles, and the micellar stability and drug carrying ability were investigated. The size and the morphology of the cargo-loaded micelles were determined by DLS, AFM, and TEM. The Nile-Red-loaded polymeric micelles were found to be stable in the presence of both fetal bovine serum and bovine serum albumin over a 72 h period and displayed thermo-responsive in vitro drug release. The blank micelles showed a low cytotoxicity. As comparison, the micelles loaded with DOX showed a much higher in vitro cytotoxicity against MCF-7 human breast cancer cell line when the incubation temperature was elevated above the LCST. Confocal laser scanning microscopy was used to study the cellular uptake and showed that the DOX-loaded micelles were internalized into the cells via an endocytosis pathway. |
| doi_str_mv | 10.1021/bm300823y |
| format | Article |
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Andrew ; Biewer, Michael C ; Wang, Qian ; Stefan, Mihaela C</creator><creatorcontrib>Cheng, Yixing ; Hao, Jing ; Lee, L. Andrew ; Biewer, Michael C ; Wang, Qian ; Stefan, Mihaela C</creatorcontrib><description>A thermo-responsive poly{γ-2-[2-(2-methoxyethoxy)ethoxy]ethoxy-ε-caprolactone}-b-poly(γ-octyloxy-ε-caprolactone) (PMEEECL- b -POCTCL) diblock copolymer was synthesized by ring-opening polymerization using tin octanoate (Sn(Oct)2) catalyst and a fluorescent dansyl initiator. The PMEEECL- b -POCTCL had a lower critical solution temperature (LCST) of 38 °C, and it was employed to prepare thermally responsive micelles. Nile Red and Doxorubicin (DOX) were loaded into the micelles, and the micellar stability and drug carrying ability were investigated. The size and the morphology of the cargo-loaded micelles were determined by DLS, AFM, and TEM. The Nile-Red-loaded polymeric micelles were found to be stable in the presence of both fetal bovine serum and bovine serum albumin over a 72 h period and displayed thermo-responsive in vitro drug release. The blank micelles showed a low cytotoxicity. As comparison, the micelles loaded with DOX showed a much higher in vitro cytotoxicity against MCF-7 human breast cancer cell line when the incubation temperature was elevated above the LCST. Confocal laser scanning microscopy was used to study the cellular uptake and showed that the DOX-loaded micelles were internalized into the cells via an endocytosis pathway.</description><identifier>ISSN: 1525-7797</identifier><identifier>EISSN: 1526-4602</identifier><identifier>DOI: 10.1021/bm300823y</identifier><identifier>PMID: 22681332</identifier><language>eng</language><publisher>Washington, DC: American Chemical Society</publisher><subject>Antibiotics, Antineoplastic - pharmacokinetics ; Antibiotics, Antineoplastic - pharmacology ; Applied sciences ; Biological and medical sciences ; Cell Line, Tumor ; Cell Survival - drug effects ; Delayed-Action Preparations ; Doxorubicin - pharmacokinetics ; Doxorubicin - pharmacology ; Drug Compounding ; Endocytosis ; Exact sciences and technology ; Fluorescent Dyes ; General pharmacology ; Humans ; Hydrophobic and Hydrophilic Interactions ; Kinetics ; Light ; Medical sciences ; Micelles ; Microscopy, Atomic Force ; Microscopy, Electron, Transmission ; Nanocapsules ; Organic polymers ; Oxazines ; Particle Size ; Pharmaceutical technology. Pharmaceutical industry ; Pharmacology. Drug treatments ; Physicochemistry of polymers ; Polyesters - chemical synthesis ; Polyesters - chemistry ; Polymers with particular properties ; Preparation, kinetics, thermodynamics, mechanism and catalysts ; Scattering, Radiation ; Surface-Active Agents - chemical synthesis ; Surface-Active Agents - chemistry ; Temperature</subject><ispartof>Biomacromolecules, 2012-07, Vol.13 (7), p.2163-2173</ispartof><rights>Copyright © 2012 American Chemical Society</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a378t-571bdfa7c3ec833b6044b7d608df367c320a9216a48c99c1469dbc73bddf76d23</citedby><cites>FETCH-LOGICAL-a378t-571bdfa7c3ec833b6044b7d608df367c320a9216a48c99c1469dbc73bddf76d23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/bm300823y$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/bm300823y$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,776,780,2752,27053,27901,27902,56713,56763</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26144746$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22681332$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cheng, Yixing</creatorcontrib><creatorcontrib>Hao, Jing</creatorcontrib><creatorcontrib>Lee, L. Andrew</creatorcontrib><creatorcontrib>Biewer, Michael C</creatorcontrib><creatorcontrib>Wang, Qian</creatorcontrib><creatorcontrib>Stefan, Mihaela C</creatorcontrib><title>Thermally Controlled Release of Anticancer Drug from Self-Assembled γ-Substituted Amphiphilic Poly(ε-caprolactone) Micellar Nanoparticles</title><title>Biomacromolecules</title><addtitle>Biomacromolecules</addtitle><description>A thermo-responsive poly{γ-2-[2-(2-methoxyethoxy)ethoxy]ethoxy-ε-caprolactone}-b-poly(γ-octyloxy-ε-caprolactone) (PMEEECL- b -POCTCL) diblock copolymer was synthesized by ring-opening polymerization using tin octanoate (Sn(Oct)2) catalyst and a fluorescent dansyl initiator. The PMEEECL- b -POCTCL had a lower critical solution temperature (LCST) of 38 °C, and it was employed to prepare thermally responsive micelles. Nile Red and Doxorubicin (DOX) were loaded into the micelles, and the micellar stability and drug carrying ability were investigated. The size and the morphology of the cargo-loaded micelles were determined by DLS, AFM, and TEM. The Nile-Red-loaded polymeric micelles were found to be stable in the presence of both fetal bovine serum and bovine serum albumin over a 72 h period and displayed thermo-responsive in vitro drug release. The blank micelles showed a low cytotoxicity. As comparison, the micelles loaded with DOX showed a much higher in vitro cytotoxicity against MCF-7 human breast cancer cell line when the incubation temperature was elevated above the LCST. Confocal laser scanning microscopy was used to study the cellular uptake and showed that the DOX-loaded micelles were internalized into the cells via an endocytosis pathway.</description><subject>Antibiotics, Antineoplastic - pharmacokinetics</subject><subject>Antibiotics, Antineoplastic - pharmacology</subject><subject>Applied sciences</subject><subject>Biological and medical sciences</subject><subject>Cell Line, Tumor</subject><subject>Cell Survival - drug effects</subject><subject>Delayed-Action Preparations</subject><subject>Doxorubicin - pharmacokinetics</subject><subject>Doxorubicin - pharmacology</subject><subject>Drug Compounding</subject><subject>Endocytosis</subject><subject>Exact sciences and technology</subject><subject>Fluorescent Dyes</subject><subject>General pharmacology</subject><subject>Humans</subject><subject>Hydrophobic and Hydrophilic Interactions</subject><subject>Kinetics</subject><subject>Light</subject><subject>Medical sciences</subject><subject>Micelles</subject><subject>Microscopy, Atomic Force</subject><subject>Microscopy, Electron, Transmission</subject><subject>Nanocapsules</subject><subject>Organic polymers</subject><subject>Oxazines</subject><subject>Particle Size</subject><subject>Pharmaceutical technology. Pharmaceutical industry</subject><subject>Pharmacology. Drug treatments</subject><subject>Physicochemistry of polymers</subject><subject>Polyesters - chemical synthesis</subject><subject>Polyesters - chemistry</subject><subject>Polymers with particular properties</subject><subject>Preparation, kinetics, thermodynamics, mechanism and catalysts</subject><subject>Scattering, Radiation</subject><subject>Surface-Active Agents - chemical synthesis</subject><subject>Surface-Active Agents - chemistry</subject><subject>Temperature</subject><issn>1525-7797</issn><issn>1526-4602</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqN0UtOHDEQAFALJQqfsOACkTeRYNGJf213L0eTAJHIRwHWLX_KoZG7PdjdizlDjhNxDc6EgQlssohkyS7rqapUhdABJR8oYfSjGTghDePrLbRDayYrIQl79fiuK6VatY12c74mhLRc1G_QNmOyoZyzHfT74grSoENY42UcpxRDAId_QgCdAUePF-PUWz1aSPhTmn9hn-KAzyH4apEzDOaB3_2pzmeTp36apxIuhtVVX07oLf4Rw_rw7rayelVyazvFEY7w195CCDrhb3qMK51KiQD5LXrtdciwv7n30OXx54vlaXX2_eTLcnFWaa6aqaoVNc5rZTnYhnMjiRBGOUka57ks34zollGpRWPb1lIhW2es4sY5r6RjfA8dPuUtLd3MkKdu6PNjQyPEOXdlbIK3tRT_QUmhNeFEFnr0RG2KOSfw3Sr1g07rgh4c7Z7XVOy7TdrZDOCe5d-9FPB-A3S2OvhUNtDnFyepEErIF6dt7q7jnMYyuH8UvAf1A6kM</recordid><startdate>20120709</startdate><enddate>20120709</enddate><creator>Cheng, Yixing</creator><creator>Hao, Jing</creator><creator>Lee, L. 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Andrew ; Biewer, Michael C ; Wang, Qian ; Stefan, Mihaela C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a378t-571bdfa7c3ec833b6044b7d608df367c320a9216a48c99c1469dbc73bddf76d23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Antibiotics, Antineoplastic - pharmacokinetics</topic><topic>Antibiotics, Antineoplastic - pharmacology</topic><topic>Applied sciences</topic><topic>Biological and medical sciences</topic><topic>Cell Line, Tumor</topic><topic>Cell Survival - drug effects</topic><topic>Delayed-Action Preparations</topic><topic>Doxorubicin - pharmacokinetics</topic><topic>Doxorubicin - pharmacology</topic><topic>Drug Compounding</topic><topic>Endocytosis</topic><topic>Exact sciences and technology</topic><topic>Fluorescent Dyes</topic><topic>General pharmacology</topic><topic>Humans</topic><topic>Hydrophobic and Hydrophilic Interactions</topic><topic>Kinetics</topic><topic>Light</topic><topic>Medical sciences</topic><topic>Micelles</topic><topic>Microscopy, Atomic Force</topic><topic>Microscopy, Electron, Transmission</topic><topic>Nanocapsules</topic><topic>Organic polymers</topic><topic>Oxazines</topic><topic>Particle Size</topic><topic>Pharmaceutical technology. Pharmaceutical industry</topic><topic>Pharmacology. Drug treatments</topic><topic>Physicochemistry of polymers</topic><topic>Polyesters - chemical synthesis</topic><topic>Polyesters - chemistry</topic><topic>Polymers with particular properties</topic><topic>Preparation, kinetics, thermodynamics, mechanism and catalysts</topic><topic>Scattering, Radiation</topic><topic>Surface-Active Agents - chemical synthesis</topic><topic>Surface-Active Agents - chemistry</topic><topic>Temperature</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cheng, Yixing</creatorcontrib><creatorcontrib>Hao, Jing</creatorcontrib><creatorcontrib>Lee, L. Andrew</creatorcontrib><creatorcontrib>Biewer, Michael C</creatorcontrib><creatorcontrib>Wang, Qian</creatorcontrib><creatorcontrib>Stefan, Mihaela C</creatorcontrib><collection>Pascal-Francis</collection><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><jtitle>Biomacromolecules</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cheng, Yixing</au><au>Hao, Jing</au><au>Lee, L. Andrew</au><au>Biewer, Michael C</au><au>Wang, Qian</au><au>Stefan, Mihaela C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Thermally Controlled Release of Anticancer Drug from Self-Assembled γ-Substituted Amphiphilic Poly(ε-caprolactone) Micellar Nanoparticles</atitle><jtitle>Biomacromolecules</jtitle><addtitle>Biomacromolecules</addtitle><date>2012-07-09</date><risdate>2012</risdate><volume>13</volume><issue>7</issue><spage>2163</spage><epage>2173</epage><pages>2163-2173</pages><issn>1525-7797</issn><eissn>1526-4602</eissn><abstract>A thermo-responsive poly{γ-2-[2-(2-methoxyethoxy)ethoxy]ethoxy-ε-caprolactone}-b-poly(γ-octyloxy-ε-caprolactone) (PMEEECL- b -POCTCL) diblock copolymer was synthesized by ring-opening polymerization using tin octanoate (Sn(Oct)2) catalyst and a fluorescent dansyl initiator. The PMEEECL- b -POCTCL had a lower critical solution temperature (LCST) of 38 °C, and it was employed to prepare thermally responsive micelles. Nile Red and Doxorubicin (DOX) were loaded into the micelles, and the micellar stability and drug carrying ability were investigated. The size and the morphology of the cargo-loaded micelles were determined by DLS, AFM, and TEM. The Nile-Red-loaded polymeric micelles were found to be stable in the presence of both fetal bovine serum and bovine serum albumin over a 72 h period and displayed thermo-responsive in vitro drug release. The blank micelles showed a low cytotoxicity. As comparison, the micelles loaded with DOX showed a much higher in vitro cytotoxicity against MCF-7 human breast cancer cell line when the incubation temperature was elevated above the LCST. Confocal laser scanning microscopy was used to study the cellular uptake and showed that the DOX-loaded micelles were internalized into the cells via an endocytosis pathway.</abstract><cop>Washington, DC</cop><pub>American Chemical Society</pub><pmid>22681332</pmid><doi>10.1021/bm300823y</doi><tpages>11</tpages></addata></record> |
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| subjects | Antibiotics, Antineoplastic - pharmacokinetics Antibiotics, Antineoplastic - pharmacology Applied sciences Biological and medical sciences Cell Line, Tumor Cell Survival - drug effects Delayed-Action Preparations Doxorubicin - pharmacokinetics Doxorubicin - pharmacology Drug Compounding Endocytosis Exact sciences and technology Fluorescent Dyes General pharmacology Humans Hydrophobic and Hydrophilic Interactions Kinetics Light Medical sciences Micelles Microscopy, Atomic Force Microscopy, Electron, Transmission Nanocapsules Organic polymers Oxazines Particle Size Pharmaceutical technology. Pharmaceutical industry Pharmacology. Drug treatments Physicochemistry of polymers Polyesters - chemical synthesis Polyesters - chemistry Polymers with particular properties Preparation, kinetics, thermodynamics, mechanism and catalysts Scattering, Radiation Surface-Active Agents - chemical synthesis Surface-Active Agents - chemistry Temperature |
| title | Thermally Controlled Release of Anticancer Drug from Self-Assembled γ-Substituted Amphiphilic Poly(ε-caprolactone) Micellar Nanoparticles |
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