Acid and reduction stimulated logic “and”-type combinational release mode achieved in DOX-loaded superparamagnetic nanogel
A superparamagnetic nanogel featured with a logic “and”-type pH/reduction combinational stimulated release mode was fabricated as a drug delivery system by virtue of parallel crosslinking. The disulfide bond and electrostatic interaction between thiolated alginate (SA–SH) and thiolated/aminated iron...
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Veröffentlicht in: | Materials Science & Engineering C 2016-08, Vol.65, p.354-363 |
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creator | Song, Meifang Xue, Yanan Chen, Lidi Xia, Xiaoyang Zhou, Yang Liu, Lei Yu, Bo Long, Sihui Huang, Shiwen Yu, Faquan |
description | A superparamagnetic nanogel featured with a logic “and”-type pH/reduction combinational stimulated release mode was fabricated as a drug delivery system by virtue of parallel crosslinking. The disulfide bond and electrostatic interaction between thiolated alginate (SA–SH) and thiolated/aminated iron oxide nanoparticles (SH–MION–NH2) were employed to achieve the mechanism. The obtained DOX-loaded magnetic nanogel is 122.7±20.3nm in size with superparamagnetism. The combinational conditions of pH5.0/10mM glutathione (GSH) stimulated a significantly high accumulative release. However, either pH7.4/10mM (GSH) or pH5.0 alone induced much low release. This verified the typical logic “and”-type combinationally stimulated release mode. In vitro cytotoxicity tests clearly illustrated the effective selectivity of killing the human cervical cancer cells (HeLa) with IC50 of 1.01μg/mL and the human hepatoma cells (HepG2) with IC50 of 1.57μg/mL but significantly low cytotoxicity to the cercopithecus aethiops kidney cells (Vero). CLSM presented the internationalization of the nanogel into cytoplasm and nuclei with time. In vivo investigation revealed that the selective intratumoral accumulation and antitumor efficacy were considerably advantageous over free DOX whereas low systemic toxicity exhibited up-regulated security as compared to free DOX. Overall, the DOX-loaded magnetic nanogel with enhanced antitumor efficacy and down-regulated adverse effect was a promising nanoplatform for the clinical chemotherapy of malignancy. |
doi_str_mv | 10.1016/j.msec.2016.04.029 |
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The disulfide bond and electrostatic interaction between thiolated alginate (SA–SH) and thiolated/aminated iron oxide nanoparticles (SH–MION–NH2) were employed to achieve the mechanism. The obtained DOX-loaded magnetic nanogel is 122.7±20.3nm in size with superparamagnetism. The combinational conditions of pH5.0/10mM glutathione (GSH) stimulated a significantly high accumulative release. However, either pH7.4/10mM (GSH) or pH5.0 alone induced much low release. This verified the typical logic “and”-type combinationally stimulated release mode. In vitro cytotoxicity tests clearly illustrated the effective selectivity of killing the human cervical cancer cells (HeLa) with IC50 of 1.01μg/mL and the human hepatoma cells (HepG2) with IC50 of 1.57μg/mL but significantly low cytotoxicity to the cercopithecus aethiops kidney cells (Vero). CLSM presented the internationalization of the nanogel into cytoplasm and nuclei with time. In vivo investigation revealed that the selective intratumoral accumulation and antitumor efficacy were considerably advantageous over free DOX whereas low systemic toxicity exhibited up-regulated security as compared to free DOX. Overall, the DOX-loaded magnetic nanogel with enhanced antitumor efficacy and down-regulated adverse effect was a promising nanoplatform for the clinical chemotherapy of malignancy.</description><identifier>ISSN: 0928-4931</identifier><identifier>EISSN: 1873-0191</identifier><identifier>DOI: 10.1016/j.msec.2016.04.029</identifier><identifier>PMID: 27157762</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Alginates - chemistry ; Animals ; Antibiotics, Antineoplastic - administration & dosage ; Antibiotics, Antineoplastic - chemistry ; Antibiotics, Antineoplastic - pharmacology ; Anticancer properties ; Cell Survival - drug effects ; Cercopithecus aethiops ; Combinational stimulation ; Controlled release ; Doxorubicin - administration & dosage ; Doxorubicin - chemistry ; Doxorubicin - pharmacology ; Drug Carriers - chemistry ; Effectiveness ; Glucuronic Acid - chemistry ; Glutathione - chemistry ; HeLa Cells ; Hep G2 Cells ; Hexuronic Acids - chemistry ; Human ; Humans ; Hydrogen-Ion Concentration ; In vivo methods and tests ; Liver Neoplasms - drug therapy ; Liver Neoplasms - pathology ; Logic ; Magnetics ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Microscopy, Confocal ; Nanogel ; Nanostructure ; Particle Size ; pH/reduction responsiveness ; Polyethylene Glycols - chemistry ; Polyethyleneimine - chemistry ; Reduction ; Spectroscopy, Fourier Transform Infrared ; Superparamagnetism ; Toxicity ; Transplantation, Heterologous ; Vero Cells</subject><ispartof>Materials Science & Engineering C, 2016-08, Vol.65, p.354-363</ispartof><rights>2016 Elsevier B.V.</rights><rights>Copyright © 2016 Elsevier B.V. All rights reserved.</rights><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c426t-7fb587708f2f736a91d97a2b5a32d31271aaf050a4f8e00760fdd504beeeeb0d3</citedby><cites>FETCH-LOGICAL-c426t-7fb587708f2f736a91d97a2b5a32d31271aaf050a4f8e00760fdd504beeeeb0d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.msec.2016.04.029$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,777,781,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27157762$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Song, Meifang</creatorcontrib><creatorcontrib>Xue, Yanan</creatorcontrib><creatorcontrib>Chen, Lidi</creatorcontrib><creatorcontrib>Xia, Xiaoyang</creatorcontrib><creatorcontrib>Zhou, Yang</creatorcontrib><creatorcontrib>Liu, Lei</creatorcontrib><creatorcontrib>Yu, Bo</creatorcontrib><creatorcontrib>Long, Sihui</creatorcontrib><creatorcontrib>Huang, Shiwen</creatorcontrib><creatorcontrib>Yu, Faquan</creatorcontrib><title>Acid and reduction stimulated logic “and”-type combinational release mode achieved in DOX-loaded superparamagnetic nanogel</title><title>Materials Science & Engineering C</title><addtitle>Mater Sci Eng C Mater Biol Appl</addtitle><description>A superparamagnetic nanogel featured with a logic “and”-type pH/reduction combinational stimulated release mode was fabricated as a drug delivery system by virtue of parallel crosslinking. The disulfide bond and electrostatic interaction between thiolated alginate (SA–SH) and thiolated/aminated iron oxide nanoparticles (SH–MION–NH2) were employed to achieve the mechanism. The obtained DOX-loaded magnetic nanogel is 122.7±20.3nm in size with superparamagnetism. The combinational conditions of pH5.0/10mM glutathione (GSH) stimulated a significantly high accumulative release. However, either pH7.4/10mM (GSH) or pH5.0 alone induced much low release. This verified the typical logic “and”-type combinationally stimulated release mode. In vitro cytotoxicity tests clearly illustrated the effective selectivity of killing the human cervical cancer cells (HeLa) with IC50 of 1.01μg/mL and the human hepatoma cells (HepG2) with IC50 of 1.57μg/mL but significantly low cytotoxicity to the cercopithecus aethiops kidney cells (Vero). CLSM presented the internationalization of the nanogel into cytoplasm and nuclei with time. In vivo investigation revealed that the selective intratumoral accumulation and antitumor efficacy were considerably advantageous over free DOX whereas low systemic toxicity exhibited up-regulated security as compared to free DOX. Overall, the DOX-loaded magnetic nanogel with enhanced antitumor efficacy and down-regulated adverse effect was a promising nanoplatform for the clinical chemotherapy of malignancy.</description><subject>Alginates - chemistry</subject><subject>Animals</subject><subject>Antibiotics, Antineoplastic - administration & dosage</subject><subject>Antibiotics, Antineoplastic - chemistry</subject><subject>Antibiotics, Antineoplastic - pharmacology</subject><subject>Anticancer properties</subject><subject>Cell Survival - drug effects</subject><subject>Cercopithecus aethiops</subject><subject>Combinational stimulation</subject><subject>Controlled release</subject><subject>Doxorubicin - administration & dosage</subject><subject>Doxorubicin - chemistry</subject><subject>Doxorubicin - pharmacology</subject><subject>Drug Carriers - chemistry</subject><subject>Effectiveness</subject><subject>Glucuronic Acid - chemistry</subject><subject>Glutathione - chemistry</subject><subject>HeLa Cells</subject><subject>Hep G2 Cells</subject><subject>Hexuronic Acids - chemistry</subject><subject>Human</subject><subject>Humans</subject><subject>Hydrogen-Ion Concentration</subject><subject>In vivo methods and tests</subject><subject>Liver Neoplasms - drug therapy</subject><subject>Liver Neoplasms - pathology</subject><subject>Logic</subject><subject>Magnetics</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>Microscopy, Confocal</subject><subject>Nanogel</subject><subject>Nanostructure</subject><subject>Particle Size</subject><subject>pH/reduction responsiveness</subject><subject>Polyethylene Glycols - chemistry</subject><subject>Polyethyleneimine - chemistry</subject><subject>Reduction</subject><subject>Spectroscopy, Fourier Transform Infrared</subject><subject>Superparamagnetism</subject><subject>Toxicity</subject><subject>Transplantation, Heterologous</subject><subject>Vero Cells</subject><issn>0928-4931</issn><issn>1873-0191</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMtu1TAQhi0EoofCC7BAWbJJGDsXOxKbqlylSt2AxM6a2JODj5w42EmlblAfBF6uT4KPTmHJbDyWvv-X5mPsJYeKA-_eHKopkalE3itoKhD9I7bjStYl8J4_ZjvohSqbvuZn7FlKB4BO1VI8ZWdC8lbKTuzYzwvjbIGzLSLZzawuzEVa3bR5XMkWPuydKe7vfmXi_u53ud4uVJgwDW7GI4s-5zxhomIKlgo03x3d5KCbi3fX30of0OZf2haKC0accD_TmitnnMOe_HP2ZESf6MXDe86-fnj_5fJTeXX98fPlxVVpGtGtpRyHVkkJahSjrDvsue0liqHFWtia53MQR2gBm1ERgOxgtLaFZqA8A9j6nL0-9S4x_NgorXpyyZD3OFPYkuaKd6BUreqMihNqYkgp0qiX6CaMt5qDPnrXB330ro_eNTQ6e8-hVw_92zCR_Rf5KzoDb08A5StvHEWdjKPZkHWRzKptcP_r_wMz3pg-</recordid><startdate>20160801</startdate><enddate>20160801</enddate><creator>Song, Meifang</creator><creator>Xue, Yanan</creator><creator>Chen, Lidi</creator><creator>Xia, Xiaoyang</creator><creator>Zhou, Yang</creator><creator>Liu, Lei</creator><creator>Yu, Bo</creator><creator>Long, Sihui</creator><creator>Huang, Shiwen</creator><creator>Yu, Faquan</creator><general>Elsevier B.V</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>7SR</scope><scope>7TB</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>FR3</scope><scope>JG9</scope><scope>L7M</scope></search><sort><creationdate>20160801</creationdate><title>Acid and reduction stimulated logic “and”-type combinational release mode achieved in DOX-loaded superparamagnetic nanogel</title><author>Song, Meifang ; Xue, Yanan ; Chen, Lidi ; Xia, Xiaoyang ; Zhou, Yang ; Liu, Lei ; Yu, Bo ; Long, Sihui ; Huang, Shiwen ; Yu, Faquan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c426t-7fb587708f2f736a91d97a2b5a32d31271aaf050a4f8e00760fdd504beeeeb0d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Alginates - chemistry</topic><topic>Animals</topic><topic>Antibiotics, Antineoplastic - administration & dosage</topic><topic>Antibiotics, Antineoplastic - chemistry</topic><topic>Antibiotics, Antineoplastic - pharmacology</topic><topic>Anticancer properties</topic><topic>Cell Survival - drug effects</topic><topic>Cercopithecus aethiops</topic><topic>Combinational stimulation</topic><topic>Controlled release</topic><topic>Doxorubicin - administration & dosage</topic><topic>Doxorubicin - chemistry</topic><topic>Doxorubicin - pharmacology</topic><topic>Drug Carriers - chemistry</topic><topic>Effectiveness</topic><topic>Glucuronic Acid - chemistry</topic><topic>Glutathione - chemistry</topic><topic>HeLa Cells</topic><topic>Hep G2 Cells</topic><topic>Hexuronic Acids - chemistry</topic><topic>Human</topic><topic>Humans</topic><topic>Hydrogen-Ion Concentration</topic><topic>In vivo methods and tests</topic><topic>Liver Neoplasms - drug therapy</topic><topic>Liver Neoplasms - pathology</topic><topic>Logic</topic><topic>Magnetics</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Nude</topic><topic>Microscopy, Confocal</topic><topic>Nanogel</topic><topic>Nanostructure</topic><topic>Particle Size</topic><topic>pH/reduction responsiveness</topic><topic>Polyethylene Glycols - chemistry</topic><topic>Polyethyleneimine - chemistry</topic><topic>Reduction</topic><topic>Spectroscopy, Fourier Transform Infrared</topic><topic>Superparamagnetism</topic><topic>Toxicity</topic><topic>Transplantation, Heterologous</topic><topic>Vero Cells</topic><toplevel>online_resources</toplevel><creatorcontrib>Song, Meifang</creatorcontrib><creatorcontrib>Xue, Yanan</creatorcontrib><creatorcontrib>Chen, Lidi</creatorcontrib><creatorcontrib>Xia, Xiaoyang</creatorcontrib><creatorcontrib>Zhou, Yang</creatorcontrib><creatorcontrib>Liu, Lei</creatorcontrib><creatorcontrib>Yu, Bo</creatorcontrib><creatorcontrib>Long, Sihui</creatorcontrib><creatorcontrib>Huang, Shiwen</creatorcontrib><creatorcontrib>Yu, Faquan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Engineered Materials Abstracts</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Materials Research Database</collection><collection>Advanced Technologies Database with Aerospace</collection><jtitle>Materials Science & Engineering C</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Song, Meifang</au><au>Xue, Yanan</au><au>Chen, Lidi</au><au>Xia, Xiaoyang</au><au>Zhou, Yang</au><au>Liu, Lei</au><au>Yu, Bo</au><au>Long, Sihui</au><au>Huang, Shiwen</au><au>Yu, Faquan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Acid and reduction stimulated logic “and”-type combinational release mode achieved in DOX-loaded superparamagnetic nanogel</atitle><jtitle>Materials Science & Engineering C</jtitle><addtitle>Mater Sci Eng C Mater Biol Appl</addtitle><date>2016-08-01</date><risdate>2016</risdate><volume>65</volume><spage>354</spage><epage>363</epage><pages>354-363</pages><issn>0928-4931</issn><eissn>1873-0191</eissn><abstract>A superparamagnetic nanogel featured with a logic “and”-type pH/reduction combinational stimulated release mode was fabricated as a drug delivery system by virtue of parallel crosslinking. The disulfide bond and electrostatic interaction between thiolated alginate (SA–SH) and thiolated/aminated iron oxide nanoparticles (SH–MION–NH2) were employed to achieve the mechanism. The obtained DOX-loaded magnetic nanogel is 122.7±20.3nm in size with superparamagnetism. The combinational conditions of pH5.0/10mM glutathione (GSH) stimulated a significantly high accumulative release. However, either pH7.4/10mM (GSH) or pH5.0 alone induced much low release. This verified the typical logic “and”-type combinationally stimulated release mode. In vitro cytotoxicity tests clearly illustrated the effective selectivity of killing the human cervical cancer cells (HeLa) with IC50 of 1.01μg/mL and the human hepatoma cells (HepG2) with IC50 of 1.57μg/mL but significantly low cytotoxicity to the cercopithecus aethiops kidney cells (Vero). CLSM presented the internationalization of the nanogel into cytoplasm and nuclei with time. In vivo investigation revealed that the selective intratumoral accumulation and antitumor efficacy were considerably advantageous over free DOX whereas low systemic toxicity exhibited up-regulated security as compared to free DOX. Overall, the DOX-loaded magnetic nanogel with enhanced antitumor efficacy and down-regulated adverse effect was a promising nanoplatform for the clinical chemotherapy of malignancy.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>27157762</pmid><doi>10.1016/j.msec.2016.04.029</doi><tpages>10</tpages></addata></record> |
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subjects | Alginates - chemistry Animals Antibiotics, Antineoplastic - administration & dosage Antibiotics, Antineoplastic - chemistry Antibiotics, Antineoplastic - pharmacology Anticancer properties Cell Survival - drug effects Cercopithecus aethiops Combinational stimulation Controlled release Doxorubicin - administration & dosage Doxorubicin - chemistry Doxorubicin - pharmacology Drug Carriers - chemistry Effectiveness Glucuronic Acid - chemistry Glutathione - chemistry HeLa Cells Hep G2 Cells Hexuronic Acids - chemistry Human Humans Hydrogen-Ion Concentration In vivo methods and tests Liver Neoplasms - drug therapy Liver Neoplasms - pathology Logic Magnetics Mice Mice, Inbred BALB C Mice, Nude Microscopy, Confocal Nanogel Nanostructure Particle Size pH/reduction responsiveness Polyethylene Glycols - chemistry Polyethyleneimine - chemistry Reduction Spectroscopy, Fourier Transform Infrared Superparamagnetism Toxicity Transplantation, Heterologous Vero Cells |
title | Acid and reduction stimulated logic “and”-type combinational release mode achieved in DOX-loaded superparamagnetic nanogel |
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