In vitro photodynamic effects of scavenger receptor targeted-photoactivatable nanoagents on activated macrophages
•Photoactivatable nanoagents for targeting SR-A on activated macrophages were prepared.•Ce6/DS-DOCA efficiently generated the singlet oxygen under light irradiation.•Ce6/DS-DOCA specifically targeted the activated macrophages.•Ce6/DS-DOCA caused cell death of activated macrophages after light irradi...
Gespeichert in:
| Veröffentlicht in: | International journal of biological macromolecules 2017-04, Vol.97, p.181-189 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 189 |
|---|---|
| container_issue | |
| container_start_page | 181 |
| container_title | International journal of biological macromolecules |
| container_volume | 97 |
| creator | Yi, Bong Gu Park, Ok Kyu Jeong, Myeong Seon Kwon, Seung Hae Jung, Jae In Lee, Seongsoo Ryoo, Sungwoo Kim, Sung Eun Kim, Jin Won Moon, Won-Jin Park, Kyeongsoon |
| description | •Photoactivatable nanoagents for targeting SR-A on activated macrophages were prepared.•Ce6/DS-DOCA efficiently generated the singlet oxygen under light irradiation.•Ce6/DS-DOCA specifically targeted the activated macrophages.•Ce6/DS-DOCA caused cell death of activated macrophages after light irradiation.
Scavenger receptors (SRs) expressed on the activated macrophages in inflammation sites have been considered as the most interesting and important target biomarker for targeted drug delivery, imaging and therapy. In the present study, we fabricated the scavenger receptor-A (SR-A) targeted-photoactivatable nanoagents (termed as Ce6/DS-DOCA) by entrapping chlorin e6 (Ce6) into the amphiphilic dextran sulfate-deoxycholic acid (DS-DOCA) conjugates via physically hydrophobic interactions. Insoluble Ce6 was easily encapsulated into DS-DOCA nanoparticles by a dialysis method and the loading efficiency was approximately 51.7%. The Ce6/DS-DOCA formed nano-sized self-assembled aggregates (28.8±5.6nm in diameter), confirmed by transmission electron microscope, UV/Vis and fluorescence spectrophotometer. The Ce6/DS-DOCA nanoagents could generate highly reactive singlet oxygen under laser irradiation. Also, in vitro studies showed that they were more specifically taken up by lipopolysaccharide (LPS)-induced activated macrophages (RAW 264.7) via a SR-A-mediated endocytosis, relative to by non-activated macrophages, and notably induced cell death of activated macrophages under laser irradiation. Therefore, SR-A targetable and photoactivatable Ce6/DS-DOCA nanoagents with more selective targeting to the activated macrophages will have great potential for treatment of inflammatory diseases. |
| doi_str_mv | 10.1016/j.ijbiomac.2017.01.037 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1861455600</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0141813016320402</els_id><sourcerecordid>1861455600</sourcerecordid><originalsourceid>FETCH-LOGICAL-c434t-704051ec7020c5ef19bf18f926909a105110f5cc31239216cd3dd80611f5b13f3</originalsourceid><addsrcrecordid>eNqFkEtvEzEUhS0EoiHwFyov2cxw73ieO1DFo1IlNrC2PPZ16ihjT20nUv89DknZ4s2VfM65j4-xW4QaAftP-9rtZxcWpesGcKgBaxDDK7bBcZgqABCv2QawxWpEATfsXUr78tt3OL5lN80IY1Pehj3de35yOQa-PoYczLNXi9OcrCWdEw-WJ61O5HcUeSRNaw6RZxV3lMlUfzNKZ3dSWc0H4l75oHbkz1HPrwoZXvaMYX0sUnrP3lh1SPThWrfs97evv-5-VA8_v9_ffXmodCvaXA3QQoekB2hAd2Rxmi2Odmr6CSaFRUOwndYCGzE12GsjjBmhR7TdjMKKLft46bvG8HSklOXikqbDQXkKxyRx7LHtur6g2rL-Yi1LphTJyjW6RcVniSDPuOVevuCWZ9wSUBbcJXh7nXGcFzL_Yi98i-HzxUDl0pOjKJN25DUZV2hmaYL734w_EZCWDg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1861455600</pqid></control><display><type>article</type><title>In vitro photodynamic effects of scavenger receptor targeted-photoactivatable nanoagents on activated macrophages</title><source>MEDLINE</source><source>ScienceDirect Journals (5 years ago - present)</source><creator>Yi, Bong Gu ; Park, Ok Kyu ; Jeong, Myeong Seon ; Kwon, Seung Hae ; Jung, Jae In ; Lee, Seongsoo ; Ryoo, Sungwoo ; Kim, Sung Eun ; Kim, Jin Won ; Moon, Won-Jin ; Park, Kyeongsoon</creator><creatorcontrib>Yi, Bong Gu ; Park, Ok Kyu ; Jeong, Myeong Seon ; Kwon, Seung Hae ; Jung, Jae In ; Lee, Seongsoo ; Ryoo, Sungwoo ; Kim, Sung Eun ; Kim, Jin Won ; Moon, Won-Jin ; Park, Kyeongsoon</creatorcontrib><description>•Photoactivatable nanoagents for targeting SR-A on activated macrophages were prepared.•Ce6/DS-DOCA efficiently generated the singlet oxygen under light irradiation.•Ce6/DS-DOCA specifically targeted the activated macrophages.•Ce6/DS-DOCA caused cell death of activated macrophages after light irradiation.
Scavenger receptors (SRs) expressed on the activated macrophages in inflammation sites have been considered as the most interesting and important target biomarker for targeted drug delivery, imaging and therapy. In the present study, we fabricated the scavenger receptor-A (SR-A) targeted-photoactivatable nanoagents (termed as Ce6/DS-DOCA) by entrapping chlorin e6 (Ce6) into the amphiphilic dextran sulfate-deoxycholic acid (DS-DOCA) conjugates via physically hydrophobic interactions. Insoluble Ce6 was easily encapsulated into DS-DOCA nanoparticles by a dialysis method and the loading efficiency was approximately 51.7%. The Ce6/DS-DOCA formed nano-sized self-assembled aggregates (28.8±5.6nm in diameter), confirmed by transmission electron microscope, UV/Vis and fluorescence spectrophotometer. The Ce6/DS-DOCA nanoagents could generate highly reactive singlet oxygen under laser irradiation. Also, in vitro studies showed that they were more specifically taken up by lipopolysaccharide (LPS)-induced activated macrophages (RAW 264.7) via a SR-A-mediated endocytosis, relative to by non-activated macrophages, and notably induced cell death of activated macrophages under laser irradiation. Therefore, SR-A targetable and photoactivatable Ce6/DS-DOCA nanoagents with more selective targeting to the activated macrophages will have great potential for treatment of inflammatory diseases.</description><identifier>ISSN: 0141-8130</identifier><identifier>EISSN: 1879-0003</identifier><identifier>DOI: 10.1016/j.ijbiomac.2017.01.037</identifier><identifier>PMID: 28082222</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Activated macrophages ; Animals ; Biological Transport ; Deoxycholic Acid - chemistry ; Dextran Sulfate - chemistry ; Drug Carriers - chemistry ; Gene Expression Regulation - drug effects ; Gene Expression Regulation - radiation effects ; Hydrophobic and Hydrophilic Interactions ; Intracellular Space - metabolism ; Lipopolysaccharides - pharmacology ; Macrophage Activation - drug effects ; Macrophage Activation - radiation effects ; Macrophages - drug effects ; Macrophages - immunology ; Macrophages - radiation effects ; Mice ; Molecular Targeted Therapy ; Nanoparticles - chemistry ; Photoactivatable nanoagents ; Photochemotherapy ; Porphyrins - chemistry ; Porphyrins - metabolism ; Porphyrins - pharmacology ; RAW 264.7 Cells ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Scavenger receptor targeting ; Scavenger Receptors, Class A - genetics ; Scavenger Receptors, Class A - metabolism ; Solubility</subject><ispartof>International journal of biological macromolecules, 2017-04, Vol.97, p.181-189</ispartof><rights>2017 Elsevier B.V.</rights><rights>Copyright © 2017 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c434t-704051ec7020c5ef19bf18f926909a105110f5cc31239216cd3dd80611f5b13f3</citedby><cites>FETCH-LOGICAL-c434t-704051ec7020c5ef19bf18f926909a105110f5cc31239216cd3dd80611f5b13f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ijbiomac.2017.01.037$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,781,785,3551,27928,27929,45999</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28082222$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yi, Bong Gu</creatorcontrib><creatorcontrib>Park, Ok Kyu</creatorcontrib><creatorcontrib>Jeong, Myeong Seon</creatorcontrib><creatorcontrib>Kwon, Seung Hae</creatorcontrib><creatorcontrib>Jung, Jae In</creatorcontrib><creatorcontrib>Lee, Seongsoo</creatorcontrib><creatorcontrib>Ryoo, Sungwoo</creatorcontrib><creatorcontrib>Kim, Sung Eun</creatorcontrib><creatorcontrib>Kim, Jin Won</creatorcontrib><creatorcontrib>Moon, Won-Jin</creatorcontrib><creatorcontrib>Park, Kyeongsoon</creatorcontrib><title>In vitro photodynamic effects of scavenger receptor targeted-photoactivatable nanoagents on activated macrophages</title><title>International journal of biological macromolecules</title><addtitle>Int J Biol Macromol</addtitle><description>•Photoactivatable nanoagents for targeting SR-A on activated macrophages were prepared.•Ce6/DS-DOCA efficiently generated the singlet oxygen under light irradiation.•Ce6/DS-DOCA specifically targeted the activated macrophages.•Ce6/DS-DOCA caused cell death of activated macrophages after light irradiation.
Scavenger receptors (SRs) expressed on the activated macrophages in inflammation sites have been considered as the most interesting and important target biomarker for targeted drug delivery, imaging and therapy. In the present study, we fabricated the scavenger receptor-A (SR-A) targeted-photoactivatable nanoagents (termed as Ce6/DS-DOCA) by entrapping chlorin e6 (Ce6) into the amphiphilic dextran sulfate-deoxycholic acid (DS-DOCA) conjugates via physically hydrophobic interactions. Insoluble Ce6 was easily encapsulated into DS-DOCA nanoparticles by a dialysis method and the loading efficiency was approximately 51.7%. The Ce6/DS-DOCA formed nano-sized self-assembled aggregates (28.8±5.6nm in diameter), confirmed by transmission electron microscope, UV/Vis and fluorescence spectrophotometer. The Ce6/DS-DOCA nanoagents could generate highly reactive singlet oxygen under laser irradiation. Also, in vitro studies showed that they were more specifically taken up by lipopolysaccharide (LPS)-induced activated macrophages (RAW 264.7) via a SR-A-mediated endocytosis, relative to by non-activated macrophages, and notably induced cell death of activated macrophages under laser irradiation. Therefore, SR-A targetable and photoactivatable Ce6/DS-DOCA nanoagents with more selective targeting to the activated macrophages will have great potential for treatment of inflammatory diseases.</description><subject>Activated macrophages</subject><subject>Animals</subject><subject>Biological Transport</subject><subject>Deoxycholic Acid - chemistry</subject><subject>Dextran Sulfate - chemistry</subject><subject>Drug Carriers - chemistry</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Gene Expression Regulation - radiation effects</subject><subject>Hydrophobic and Hydrophilic Interactions</subject><subject>Intracellular Space - metabolism</subject><subject>Lipopolysaccharides - pharmacology</subject><subject>Macrophage Activation - drug effects</subject><subject>Macrophage Activation - radiation effects</subject><subject>Macrophages - drug effects</subject><subject>Macrophages - immunology</subject><subject>Macrophages - radiation effects</subject><subject>Mice</subject><subject>Molecular Targeted Therapy</subject><subject>Nanoparticles - chemistry</subject><subject>Photoactivatable nanoagents</subject><subject>Photochemotherapy</subject><subject>Porphyrins - chemistry</subject><subject>Porphyrins - metabolism</subject><subject>Porphyrins - pharmacology</subject><subject>RAW 264.7 Cells</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Scavenger receptor targeting</subject><subject>Scavenger Receptors, Class A - genetics</subject><subject>Scavenger Receptors, Class A - metabolism</subject><subject>Solubility</subject><issn>0141-8130</issn><issn>1879-0003</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkEtvEzEUhS0EoiHwFyov2cxw73ieO1DFo1IlNrC2PPZ16ihjT20nUv89DknZ4s2VfM65j4-xW4QaAftP-9rtZxcWpesGcKgBaxDDK7bBcZgqABCv2QawxWpEATfsXUr78tt3OL5lN80IY1Pehj3de35yOQa-PoYczLNXi9OcrCWdEw-WJ61O5HcUeSRNaw6RZxV3lMlUfzNKZ3dSWc0H4l75oHbkz1HPrwoZXvaMYX0sUnrP3lh1SPThWrfs97evv-5-VA8_v9_ffXmodCvaXA3QQoekB2hAd2Rxmi2Odmr6CSaFRUOwndYCGzE12GsjjBmhR7TdjMKKLft46bvG8HSklOXikqbDQXkKxyRx7LHtur6g2rL-Yi1LphTJyjW6RcVniSDPuOVevuCWZ9wSUBbcJXh7nXGcFzL_Yi98i-HzxUDl0pOjKJN25DUZV2hmaYL734w_EZCWDg</recordid><startdate>201704</startdate><enddate>201704</enddate><creator>Yi, Bong Gu</creator><creator>Park, Ok Kyu</creator><creator>Jeong, Myeong Seon</creator><creator>Kwon, Seung Hae</creator><creator>Jung, Jae In</creator><creator>Lee, Seongsoo</creator><creator>Ryoo, Sungwoo</creator><creator>Kim, Sung Eun</creator><creator>Kim, Jin Won</creator><creator>Moon, Won-Jin</creator><creator>Park, Kyeongsoon</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>7X8</scope></search><sort><creationdate>201704</creationdate><title>In vitro photodynamic effects of scavenger receptor targeted-photoactivatable nanoagents on activated macrophages</title><author>Yi, Bong Gu ; Park, Ok Kyu ; Jeong, Myeong Seon ; Kwon, Seung Hae ; Jung, Jae In ; Lee, Seongsoo ; Ryoo, Sungwoo ; Kim, Sung Eun ; Kim, Jin Won ; Moon, Won-Jin ; Park, Kyeongsoon</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c434t-704051ec7020c5ef19bf18f926909a105110f5cc31239216cd3dd80611f5b13f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Activated macrophages</topic><topic>Animals</topic><topic>Biological Transport</topic><topic>Deoxycholic Acid - chemistry</topic><topic>Dextran Sulfate - chemistry</topic><topic>Drug Carriers - chemistry</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Gene Expression Regulation - radiation effects</topic><topic>Hydrophobic and Hydrophilic Interactions</topic><topic>Intracellular Space - metabolism</topic><topic>Lipopolysaccharides - pharmacology</topic><topic>Macrophage Activation - drug effects</topic><topic>Macrophage Activation - radiation effects</topic><topic>Macrophages - drug effects</topic><topic>Macrophages - immunology</topic><topic>Macrophages - radiation effects</topic><topic>Mice</topic><topic>Molecular Targeted Therapy</topic><topic>Nanoparticles - chemistry</topic><topic>Photoactivatable nanoagents</topic><topic>Photochemotherapy</topic><topic>Porphyrins - chemistry</topic><topic>Porphyrins - metabolism</topic><topic>Porphyrins - pharmacology</topic><topic>RAW 264.7 Cells</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Scavenger receptor targeting</topic><topic>Scavenger Receptors, Class A - genetics</topic><topic>Scavenger Receptors, Class A - metabolism</topic><topic>Solubility</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yi, Bong Gu</creatorcontrib><creatorcontrib>Park, Ok Kyu</creatorcontrib><creatorcontrib>Jeong, Myeong Seon</creatorcontrib><creatorcontrib>Kwon, Seung Hae</creatorcontrib><creatorcontrib>Jung, Jae In</creatorcontrib><creatorcontrib>Lee, Seongsoo</creatorcontrib><creatorcontrib>Ryoo, Sungwoo</creatorcontrib><creatorcontrib>Kim, Sung Eun</creatorcontrib><creatorcontrib>Kim, Jin Won</creatorcontrib><creatorcontrib>Moon, Won-Jin</creatorcontrib><creatorcontrib>Park, Kyeongsoon</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><jtitle>International journal of biological macromolecules</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yi, Bong Gu</au><au>Park, Ok Kyu</au><au>Jeong, Myeong Seon</au><au>Kwon, Seung Hae</au><au>Jung, Jae In</au><au>Lee, Seongsoo</au><au>Ryoo, Sungwoo</au><au>Kim, Sung Eun</au><au>Kim, Jin Won</au><au>Moon, Won-Jin</au><au>Park, Kyeongsoon</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>In vitro photodynamic effects of scavenger receptor targeted-photoactivatable nanoagents on activated macrophages</atitle><jtitle>International journal of biological macromolecules</jtitle><addtitle>Int J Biol Macromol</addtitle><date>2017-04</date><risdate>2017</risdate><volume>97</volume><spage>181</spage><epage>189</epage><pages>181-189</pages><issn>0141-8130</issn><eissn>1879-0003</eissn><abstract>•Photoactivatable nanoagents for targeting SR-A on activated macrophages were prepared.•Ce6/DS-DOCA efficiently generated the singlet oxygen under light irradiation.•Ce6/DS-DOCA specifically targeted the activated macrophages.•Ce6/DS-DOCA caused cell death of activated macrophages after light irradiation.
Scavenger receptors (SRs) expressed on the activated macrophages in inflammation sites have been considered as the most interesting and important target biomarker for targeted drug delivery, imaging and therapy. In the present study, we fabricated the scavenger receptor-A (SR-A) targeted-photoactivatable nanoagents (termed as Ce6/DS-DOCA) by entrapping chlorin e6 (Ce6) into the amphiphilic dextran sulfate-deoxycholic acid (DS-DOCA) conjugates via physically hydrophobic interactions. Insoluble Ce6 was easily encapsulated into DS-DOCA nanoparticles by a dialysis method and the loading efficiency was approximately 51.7%. The Ce6/DS-DOCA formed nano-sized self-assembled aggregates (28.8±5.6nm in diameter), confirmed by transmission electron microscope, UV/Vis and fluorescence spectrophotometer. The Ce6/DS-DOCA nanoagents could generate highly reactive singlet oxygen under laser irradiation. Also, in vitro studies showed that they were more specifically taken up by lipopolysaccharide (LPS)-induced activated macrophages (RAW 264.7) via a SR-A-mediated endocytosis, relative to by non-activated macrophages, and notably induced cell death of activated macrophages under laser irradiation. Therefore, SR-A targetable and photoactivatable Ce6/DS-DOCA nanoagents with more selective targeting to the activated macrophages will have great potential for treatment of inflammatory diseases.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>28082222</pmid><doi>10.1016/j.ijbiomac.2017.01.037</doi><tpages>9</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0141-8130 |
| ispartof | International journal of biological macromolecules, 2017-04, Vol.97, p.181-189 |
| issn | 0141-8130 1879-0003 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1861455600 |
| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Activated macrophages Animals Biological Transport Deoxycholic Acid - chemistry Dextran Sulfate - chemistry Drug Carriers - chemistry Gene Expression Regulation - drug effects Gene Expression Regulation - radiation effects Hydrophobic and Hydrophilic Interactions Intracellular Space - metabolism Lipopolysaccharides - pharmacology Macrophage Activation - drug effects Macrophage Activation - radiation effects Macrophages - drug effects Macrophages - immunology Macrophages - radiation effects Mice Molecular Targeted Therapy Nanoparticles - chemistry Photoactivatable nanoagents Photochemotherapy Porphyrins - chemistry Porphyrins - metabolism Porphyrins - pharmacology RAW 264.7 Cells RNA, Messenger - genetics RNA, Messenger - metabolism Scavenger receptor targeting Scavenger Receptors, Class A - genetics Scavenger Receptors, Class A - metabolism Solubility |
| title | In vitro photodynamic effects of scavenger receptor targeted-photoactivatable nanoagents on activated macrophages |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-16T17%3A09%3A14IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=In%20vitro%20photodynamic%20effects%20of%20scavenger%20receptor%20targeted-photoactivatable%20nanoagents%20on%20activated%20macrophages&rft.jtitle=International%20journal%20of%20biological%20macromolecules&rft.au=Yi,%20Bong%20Gu&rft.date=2017-04&rft.volume=97&rft.spage=181&rft.epage=189&rft.pages=181-189&rft.issn=0141-8130&rft.eissn=1879-0003&rft_id=info:doi/10.1016/j.ijbiomac.2017.01.037&rft_dat=%3Cproquest_cross%3E1861455600%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1861455600&rft_id=info:pmid/28082222&rft_els_id=S0141813016320402&rfr_iscdi=true |