Doxorubicin-Conjugated Iron Oxide Nanoparticles Synthesized by Laser Pyrolysis: In Vitro Study on Human Breast Cancer Cells
Even today, breast cancer remains a global public problem, with a high mortality rate among women. Nanoparticle (NP) based systems are developed to enhance drug delivery, reducing the toxic effect of medicine molecules. By using iron oxide nanoparticles for cancer treatment, several advantages were...
Gespeichert in:
| Veröffentlicht in: | Polymers 2020-11, Vol.12 (12), p.2799 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | 12 |
| container_start_page | 2799 |
| container_title | Polymers |
| container_volume | 12 |
| creator | Lungu, Iulia Ioana Nistorescu, Simona Badea, Mădălina Andreea Petre, Andreea-Mihaela Udrea, Ana-Maria Banici, Ana-Maria Fleacă, Claudiu Andronescu, Ecaterina Dinischiotu, Anca Dumitrache, Florian Staicu, Angela Balaș, Mihaela |
| description | Even today, breast cancer remains a global public problem, with a high mortality rate among women. Nanoparticle (NP) based systems are developed to enhance drug delivery, reducing the toxic effect of medicine molecules. By using iron oxide nanoparticles for cancer treatment, several advantages were highlighted: the ability to target specific locations derived from their magnetic properties and reduced side effects. The aim of this study was to examine on breast cancer cell line the anticancer potential of γ-Fe
O
NPs loaded with doxorubicin (DOX) and stabilized with carboxymethylcellulose sodium (CMCNa). The γ-Fe
O
NPs were synthesized by laser pyrolysis technique and their nanometric size and crystallinity were confirmed by X-ray diffraction and transmission electron microscopy. The loading efficiency was estimated by using absorption and fluorescence spectroscopy. The DOX conjugated//CMCNa coated γ-Fe
O
NPs proved through the biological studies to have a good anticancer effect through the inhibition of tumoral cell proliferation, disruption of the cellular membrane, induction of cell death and reduced effects on normal breast cells. Our data showed that DOX cytotoxicity increases significantly when conjugated with ɣ-Fe
O
and ɣ-Fe
O
_CMCNa, a 50% reduction of cancer cell viability was obtained with a concentration around 0.1 µg/mL. |
| doi_str_mv | 10.3390/polym12122799 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7760716</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2465625851</sourcerecordid><originalsourceid>FETCH-LOGICAL-c415t-a570d0e9da0ceec8086274590ab7b5809d67493313c039c1d5d2c8e404d2c1783</originalsourceid><addsrcrecordid>eNpVkd1rFTEQxYMottQ--ioBn1cnySbZ9UHQtbUXLlao-hqySdrmsje5JtnSrf-8Kf2gnZcZmN-cOXAQekvgA2M9fNzFadkSSiiVff8C7VOQrGmZgJdP5j10mPMGarVcCCJfoz3GKBcgYB_9-xavY5pHb3xohhg284UuzuJVigGfXnvr8A8d4k6n4s3kMj5bQrl02d9UaFzwWmeX8M8lVSfZ5094FfAfX1LEZ2W2C64qJ_NWB_w1OZ0LHnQw9WBw05TfoFfnesru8L4foN_HR7-Gk2Z9-n01fFk3piW8NJpLsOB6q8E4ZzroBJUt70GPcuQd9FbItmeMMAOsN8RyS03nWmhrJ7JjB-jzne5uHrfOGhdK0pPaJb_VaVFRe_V8E_yluohXSkoBkogq8P5eIMW_s8tFbeKcQvWsaCu4oLzjpFLNHWVSzDm588cPBNRtXOpZXJV_99TWI_0QDvsPhwuS1w</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2465625851</pqid></control><display><type>article</type><title>Doxorubicin-Conjugated Iron Oxide Nanoparticles Synthesized by Laser Pyrolysis: In Vitro Study on Human Breast Cancer Cells</title><source>MDPI - Multidisciplinary Digital Publishing Institute</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>PubMed Central Open Access</source><creator>Lungu, Iulia Ioana ; Nistorescu, Simona ; Badea, Mădălina Andreea ; Petre, Andreea-Mihaela ; Udrea, Ana-Maria ; Banici, Ana-Maria ; Fleacă, Claudiu ; Andronescu, Ecaterina ; Dinischiotu, Anca ; Dumitrache, Florian ; Staicu, Angela ; Balaș, Mihaela</creator><creatorcontrib>Lungu, Iulia Ioana ; Nistorescu, Simona ; Badea, Mădălina Andreea ; Petre, Andreea-Mihaela ; Udrea, Ana-Maria ; Banici, Ana-Maria ; Fleacă, Claudiu ; Andronescu, Ecaterina ; Dinischiotu, Anca ; Dumitrache, Florian ; Staicu, Angela ; Balaș, Mihaela</creatorcontrib><description>Even today, breast cancer remains a global public problem, with a high mortality rate among women. Nanoparticle (NP) based systems are developed to enhance drug delivery, reducing the toxic effect of medicine molecules. By using iron oxide nanoparticles for cancer treatment, several advantages were highlighted: the ability to target specific locations derived from their magnetic properties and reduced side effects. The aim of this study was to examine on breast cancer cell line the anticancer potential of γ-Fe
O
NPs loaded with doxorubicin (DOX) and stabilized with carboxymethylcellulose sodium (CMCNa). The γ-Fe
O
NPs were synthesized by laser pyrolysis technique and their nanometric size and crystallinity were confirmed by X-ray diffraction and transmission electron microscopy. The loading efficiency was estimated by using absorption and fluorescence spectroscopy. The DOX conjugated//CMCNa coated γ-Fe
O
NPs proved through the biological studies to have a good anticancer effect through the inhibition of tumoral cell proliferation, disruption of the cellular membrane, induction of cell death and reduced effects on normal breast cells. Our data showed that DOX cytotoxicity increases significantly when conjugated with ɣ-Fe
O
and ɣ-Fe
O
_CMCNa, a 50% reduction of cancer cell viability was obtained with a concentration around 0.1 µg/mL.</description><identifier>ISSN: 2073-4360</identifier><identifier>EISSN: 2073-4360</identifier><identifier>DOI: 10.3390/polym12122799</identifier><identifier>PMID: 33256060</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Anticancer properties ; Biocompatibility ; Breast cancer ; Cancer therapies ; Cell death ; Cell membranes ; Chemotherapy ; Contrast agents ; Deoxyribonucleic acid ; DNA ; Doxorubicin ; Drug delivery systems ; Drugs ; Efficiency ; Fluorescence ; Iron oxides ; Lasers ; Lung cancer ; Magnetic fields ; Magnetic properties ; Nanomaterials ; Nanoparticles ; Pyrolysis ; Side effects ; Synthesis ; Toxicity ; Transmission electron microscopy ; Ultrasonic imaging ; Womens health</subject><ispartof>Polymers, 2020-11, Vol.12 (12), p.2799</ispartof><rights>2020. This work is licensed under http://creativecommons.org/licenses/by/3.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2020 by the authors. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c415t-a570d0e9da0ceec8086274590ab7b5809d67493313c039c1d5d2c8e404d2c1783</citedby><cites>FETCH-LOGICAL-c415t-a570d0e9da0ceec8086274590ab7b5809d67493313c039c1d5d2c8e404d2c1783</cites><orcidid>0000-0001-6245-3580 ; 0000-0003-0630-0314 ; 0000-0002-7659-7435 ; 0000-0001-9522-0118 ; 0000-0002-2226-5849</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760716/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760716/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33256060$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lungu, Iulia Ioana</creatorcontrib><creatorcontrib>Nistorescu, Simona</creatorcontrib><creatorcontrib>Badea, Mădălina Andreea</creatorcontrib><creatorcontrib>Petre, Andreea-Mihaela</creatorcontrib><creatorcontrib>Udrea, Ana-Maria</creatorcontrib><creatorcontrib>Banici, Ana-Maria</creatorcontrib><creatorcontrib>Fleacă, Claudiu</creatorcontrib><creatorcontrib>Andronescu, Ecaterina</creatorcontrib><creatorcontrib>Dinischiotu, Anca</creatorcontrib><creatorcontrib>Dumitrache, Florian</creatorcontrib><creatorcontrib>Staicu, Angela</creatorcontrib><creatorcontrib>Balaș, Mihaela</creatorcontrib><title>Doxorubicin-Conjugated Iron Oxide Nanoparticles Synthesized by Laser Pyrolysis: In Vitro Study on Human Breast Cancer Cells</title><title>Polymers</title><addtitle>Polymers (Basel)</addtitle><description>Even today, breast cancer remains a global public problem, with a high mortality rate among women. Nanoparticle (NP) based systems are developed to enhance drug delivery, reducing the toxic effect of medicine molecules. By using iron oxide nanoparticles for cancer treatment, several advantages were highlighted: the ability to target specific locations derived from their magnetic properties and reduced side effects. The aim of this study was to examine on breast cancer cell line the anticancer potential of γ-Fe
O
NPs loaded with doxorubicin (DOX) and stabilized with carboxymethylcellulose sodium (CMCNa). The γ-Fe
O
NPs were synthesized by laser pyrolysis technique and their nanometric size and crystallinity were confirmed by X-ray diffraction and transmission electron microscopy. The loading efficiency was estimated by using absorption and fluorescence spectroscopy. The DOX conjugated//CMCNa coated γ-Fe
O
NPs proved through the biological studies to have a good anticancer effect through the inhibition of tumoral cell proliferation, disruption of the cellular membrane, induction of cell death and reduced effects on normal breast cells. Our data showed that DOX cytotoxicity increases significantly when conjugated with ɣ-Fe
O
and ɣ-Fe
O
_CMCNa, a 50% reduction of cancer cell viability was obtained with a concentration around 0.1 µg/mL.</description><subject>Anticancer properties</subject><subject>Biocompatibility</subject><subject>Breast cancer</subject><subject>Cancer therapies</subject><subject>Cell death</subject><subject>Cell membranes</subject><subject>Chemotherapy</subject><subject>Contrast agents</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>Doxorubicin</subject><subject>Drug delivery systems</subject><subject>Drugs</subject><subject>Efficiency</subject><subject>Fluorescence</subject><subject>Iron oxides</subject><subject>Lasers</subject><subject>Lung cancer</subject><subject>Magnetic fields</subject><subject>Magnetic properties</subject><subject>Nanomaterials</subject><subject>Nanoparticles</subject><subject>Pyrolysis</subject><subject>Side effects</subject><subject>Synthesis</subject><subject>Toxicity</subject><subject>Transmission electron microscopy</subject><subject>Ultrasonic imaging</subject><subject>Womens health</subject><issn>2073-4360</issn><issn>2073-4360</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>BENPR</sourceid><recordid>eNpVkd1rFTEQxYMottQ--ioBn1cnySbZ9UHQtbUXLlao-hqySdrmsje5JtnSrf-8Kf2gnZcZmN-cOXAQekvgA2M9fNzFadkSSiiVff8C7VOQrGmZgJdP5j10mPMGarVcCCJfoz3GKBcgYB_9-xavY5pHb3xohhg284UuzuJVigGfXnvr8A8d4k6n4s3kMj5bQrl02d9UaFzwWmeX8M8lVSfZ5094FfAfX1LEZ2W2C64qJ_NWB_w1OZ0LHnQw9WBw05TfoFfnesru8L4foN_HR7-Gk2Z9-n01fFk3piW8NJpLsOB6q8E4ZzroBJUt70GPcuQd9FbItmeMMAOsN8RyS03nWmhrJ7JjB-jzne5uHrfOGhdK0pPaJb_VaVFRe_V8E_yluohXSkoBkogq8P5eIMW_s8tFbeKcQvWsaCu4oLzjpFLNHWVSzDm588cPBNRtXOpZXJV_99TWI_0QDvsPhwuS1w</recordid><startdate>20201126</startdate><enddate>20201126</enddate><creator>Lungu, Iulia Ioana</creator><creator>Nistorescu, Simona</creator><creator>Badea, Mădălina Andreea</creator><creator>Petre, Andreea-Mihaela</creator><creator>Udrea, Ana-Maria</creator><creator>Banici, Ana-Maria</creator><creator>Fleacă, Claudiu</creator><creator>Andronescu, Ecaterina</creator><creator>Dinischiotu, Anca</creator><creator>Dumitrache, Florian</creator><creator>Staicu, Angela</creator><creator>Balaș, Mihaela</creator><general>MDPI AG</general><general>MDPI</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7SR</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>HCIFZ</scope><scope>JG9</scope><scope>KB.</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-6245-3580</orcidid><orcidid>https://orcid.org/0000-0003-0630-0314</orcidid><orcidid>https://orcid.org/0000-0002-7659-7435</orcidid><orcidid>https://orcid.org/0000-0001-9522-0118</orcidid><orcidid>https://orcid.org/0000-0002-2226-5849</orcidid></search><sort><creationdate>20201126</creationdate><title>Doxorubicin-Conjugated Iron Oxide Nanoparticles Synthesized by Laser Pyrolysis: In Vitro Study on Human Breast Cancer Cells</title><author>Lungu, Iulia Ioana ; Nistorescu, Simona ; Badea, Mădălina Andreea ; Petre, Andreea-Mihaela ; Udrea, Ana-Maria ; Banici, Ana-Maria ; Fleacă, Claudiu ; Andronescu, Ecaterina ; Dinischiotu, Anca ; Dumitrache, Florian ; Staicu, Angela ; Balaș, Mihaela</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c415t-a570d0e9da0ceec8086274590ab7b5809d67493313c039c1d5d2c8e404d2c1783</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Anticancer properties</topic><topic>Biocompatibility</topic><topic>Breast cancer</topic><topic>Cancer therapies</topic><topic>Cell death</topic><topic>Cell membranes</topic><topic>Chemotherapy</topic><topic>Contrast agents</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>Doxorubicin</topic><topic>Drug delivery systems</topic><topic>Drugs</topic><topic>Efficiency</topic><topic>Fluorescence</topic><topic>Iron oxides</topic><topic>Lasers</topic><topic>Lung cancer</topic><topic>Magnetic fields</topic><topic>Magnetic properties</topic><topic>Nanomaterials</topic><topic>Nanoparticles</topic><topic>Pyrolysis</topic><topic>Side effects</topic><topic>Synthesis</topic><topic>Toxicity</topic><topic>Transmission electron microscopy</topic><topic>Ultrasonic imaging</topic><topic>Womens health</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lungu, Iulia Ioana</creatorcontrib><creatorcontrib>Nistorescu, Simona</creatorcontrib><creatorcontrib>Badea, Mădălina Andreea</creatorcontrib><creatorcontrib>Petre, Andreea-Mihaela</creatorcontrib><creatorcontrib>Udrea, Ana-Maria</creatorcontrib><creatorcontrib>Banici, Ana-Maria</creatorcontrib><creatorcontrib>Fleacă, Claudiu</creatorcontrib><creatorcontrib>Andronescu, Ecaterina</creatorcontrib><creatorcontrib>Dinischiotu, Anca</creatorcontrib><creatorcontrib>Dumitrache, Florian</creatorcontrib><creatorcontrib>Staicu, Angela</creatorcontrib><creatorcontrib>Balaș, Mihaela</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Engineered Materials Abstracts</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>SciTech Premium Collection</collection><collection>Materials Research Database</collection><collection>Materials Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Polymers</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lungu, Iulia Ioana</au><au>Nistorescu, Simona</au><au>Badea, Mădălina Andreea</au><au>Petre, Andreea-Mihaela</au><au>Udrea, Ana-Maria</au><au>Banici, Ana-Maria</au><au>Fleacă, Claudiu</au><au>Andronescu, Ecaterina</au><au>Dinischiotu, Anca</au><au>Dumitrache, Florian</au><au>Staicu, Angela</au><au>Balaș, Mihaela</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Doxorubicin-Conjugated Iron Oxide Nanoparticles Synthesized by Laser Pyrolysis: In Vitro Study on Human Breast Cancer Cells</atitle><jtitle>Polymers</jtitle><addtitle>Polymers (Basel)</addtitle><date>2020-11-26</date><risdate>2020</risdate><volume>12</volume><issue>12</issue><spage>2799</spage><pages>2799-</pages><issn>2073-4360</issn><eissn>2073-4360</eissn><abstract>Even today, breast cancer remains a global public problem, with a high mortality rate among women. Nanoparticle (NP) based systems are developed to enhance drug delivery, reducing the toxic effect of medicine molecules. By using iron oxide nanoparticles for cancer treatment, several advantages were highlighted: the ability to target specific locations derived from their magnetic properties and reduced side effects. The aim of this study was to examine on breast cancer cell line the anticancer potential of γ-Fe
O
NPs loaded with doxorubicin (DOX) and stabilized with carboxymethylcellulose sodium (CMCNa). The γ-Fe
O
NPs were synthesized by laser pyrolysis technique and their nanometric size and crystallinity were confirmed by X-ray diffraction and transmission electron microscopy. The loading efficiency was estimated by using absorption and fluorescence spectroscopy. The DOX conjugated//CMCNa coated γ-Fe
O
NPs proved through the biological studies to have a good anticancer effect through the inhibition of tumoral cell proliferation, disruption of the cellular membrane, induction of cell death and reduced effects on normal breast cells. Our data showed that DOX cytotoxicity increases significantly when conjugated with ɣ-Fe
O
and ɣ-Fe
O
_CMCNa, a 50% reduction of cancer cell viability was obtained with a concentration around 0.1 µg/mL.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>33256060</pmid><doi>10.3390/polym12122799</doi><orcidid>https://orcid.org/0000-0001-6245-3580</orcidid><orcidid>https://orcid.org/0000-0003-0630-0314</orcidid><orcidid>https://orcid.org/0000-0002-7659-7435</orcidid><orcidid>https://orcid.org/0000-0001-9522-0118</orcidid><orcidid>https://orcid.org/0000-0002-2226-5849</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2073-4360 |
| ispartof | Polymers, 2020-11, Vol.12 (12), p.2799 |
| issn | 2073-4360 2073-4360 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7760716 |
| source | MDPI - Multidisciplinary Digital Publishing Institute; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; PubMed Central Open Access |
| subjects | Anticancer properties Biocompatibility Breast cancer Cancer therapies Cell death Cell membranes Chemotherapy Contrast agents Deoxyribonucleic acid DNA Doxorubicin Drug delivery systems Drugs Efficiency Fluorescence Iron oxides Lasers Lung cancer Magnetic fields Magnetic properties Nanomaterials Nanoparticles Pyrolysis Side effects Synthesis Toxicity Transmission electron microscopy Ultrasonic imaging Womens health |
| title | Doxorubicin-Conjugated Iron Oxide Nanoparticles Synthesized by Laser Pyrolysis: In Vitro Study on Human Breast Cancer Cells |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-06T14%3A51%3A05IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Doxorubicin-Conjugated%20Iron%20Oxide%20Nanoparticles%20Synthesized%20by%20Laser%20Pyrolysis:%20In%20Vitro%20Study%20on%20Human%20Breast%20Cancer%20Cells&rft.jtitle=Polymers&rft.au=Lungu,%20Iulia%20Ioana&rft.date=2020-11-26&rft.volume=12&rft.issue=12&rft.spage=2799&rft.pages=2799-&rft.issn=2073-4360&rft.eissn=2073-4360&rft_id=info:doi/10.3390/polym12122799&rft_dat=%3Cproquest_pubme%3E2465625851%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2465625851&rft_id=info:pmid/33256060&rfr_iscdi=true |