Glioblastoma cell-derived exosomes functionalized with peptides as efficient nanocarriers for synergistic chemotherapy of glioblastoma with improved biosafety
Glioblastoma (GBM) has been regarded as one of the most deadly and challenging cancers to treat with extremely poor prognosis. The limited efficacy of current chemotherapies might be attributed to the presence of glioma stem cells (GSCs) as well as the difficulties in passing through the blood–brain...
Gespeichert in:
| Veröffentlicht in: | Nano research 2023-12, Vol.16 (12), p.13283-13293 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 13293 |
|---|---|
| container_issue | 12 |
| container_start_page | 13283 |
| container_title | Nano research |
| container_volume | 16 |
| creator | Zhou, Ying Wang, Long Chen, Lufei Wu, Wei Yang, Zhimin Wang, Yuanzhuo Wang, Anqi Jiang, Sujun Qin, Xuzhen Ye, Zucheng Hu, Zhiyuan Wang, Zihua |
| description | Glioblastoma (GBM) has been regarded as one of the most deadly and challenging cancers to treat with extremely poor prognosis. The limited efficacy of current chemotherapies might be attributed to the presence of glioma stem cells (GSCs) as well as the difficulties in passing through the blood–brain barrier (BBB) and targeting tumor cells. Tumor-derived exosomes are emerging as novel and promising drug delivery systems. However, great concerns regarding the biosafety and BBB penetrability remain to be addressed. Herein, we have developed a simple and feasible strategy to engineer GBM cell-derived exosomes with improved biosafety termed “Exo@TDPs” to deliver the cargos of chemotherapeutic agents temozolomide (TMZ) and doxorubicin (DOX) into GBM tissues. Exo@TDPs decorated with angiopep-2 (Ang-2) and CD133-targeted peptides improve the capacity to penetrate the BBB and target tumor cells. Both
in vitro
and
in vivo
studies demonstrate that Exo@TDPs can cross the BBB, target GBM cells, penetrate into deep tumor parenchyma, and release the therapeutic cargos effectively. Synergistic delivery of TMZ and DOX by Exo@TDPs exerts therapeutic effects to suppress the tumor growth and prolong the survival time of orthotopic syngeneic mouse GBM models. These findings suggest that our developed Exo@TDPs loaded with chemotherapeutic drugs may bring new possibilities for the application of tumor cell-derived exosomes for brain tumor treatment. |
| doi_str_mv | 10.1007/s12274-023-5921-6 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_2908976531</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2908976531</sourcerecordid><originalsourceid>FETCH-LOGICAL-c316t-dde281ac54bcbfa6ed32ab665df897071cfc93fd2b9ffadc82d6bb332a09b6b3</originalsourceid><addsrcrecordid>eNp1UUtOwzAQjRBIlMIB2FliHbCd1kmWqIKCVIlN95Y_49ZVEgfbBcJhOCsuAcGG2cxo5n00ell2SfA1wbi8CYTScpZjWuTzmpKcHWUTUtdVjlMd_8yEzk6zsxB2GDNKZtUk-1g21slGhOhagRQ0Ta7B2xfQCN5ccC0EZPaditZ1orHvaf9q4xb10Eer01EEBMZYZaGLqBOdU8J7Cz7RnEdh6MBvbIhWIbWF1sUteNEPyBm0-ev8JWrb3ruDtbQuCANxOM9OjGgCXHz3aba-v1svHvLV0_JxcbvKVUFYzLUGWhGh5jOppBEMdEGFZGyuTVWXuCTKqLowmsraGKFVRTWTskggXEsmi2l2Ncom_-c9hMh3bu_Tw4HTGicJNi9IQpERpbwLwYPhvbet8AMnmB9S4GMKPKXADylwljh05ISE7Tbgf5X_J30CIaWRYw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2908976531</pqid></control><display><type>article</type><title>Glioblastoma cell-derived exosomes functionalized with peptides as efficient nanocarriers for synergistic chemotherapy of glioblastoma with improved biosafety</title><source>SpringerLink Journals - AutoHoldings</source><creator>Zhou, Ying ; Wang, Long ; Chen, Lufei ; Wu, Wei ; Yang, Zhimin ; Wang, Yuanzhuo ; Wang, Anqi ; Jiang, Sujun ; Qin, Xuzhen ; Ye, Zucheng ; Hu, Zhiyuan ; Wang, Zihua</creator><creatorcontrib>Zhou, Ying ; Wang, Long ; Chen, Lufei ; Wu, Wei ; Yang, Zhimin ; Wang, Yuanzhuo ; Wang, Anqi ; Jiang, Sujun ; Qin, Xuzhen ; Ye, Zucheng ; Hu, Zhiyuan ; Wang, Zihua</creatorcontrib><description>Glioblastoma (GBM) has been regarded as one of the most deadly and challenging cancers to treat with extremely poor prognosis. The limited efficacy of current chemotherapies might be attributed to the presence of glioma stem cells (GSCs) as well as the difficulties in passing through the blood–brain barrier (BBB) and targeting tumor cells. Tumor-derived exosomes are emerging as novel and promising drug delivery systems. However, great concerns regarding the biosafety and BBB penetrability remain to be addressed. Herein, we have developed a simple and feasible strategy to engineer GBM cell-derived exosomes with improved biosafety termed “Exo@TDPs” to deliver the cargos of chemotherapeutic agents temozolomide (TMZ) and doxorubicin (DOX) into GBM tissues. Exo@TDPs decorated with angiopep-2 (Ang-2) and CD133-targeted peptides improve the capacity to penetrate the BBB and target tumor cells. Both
in vitro
and
in vivo
studies demonstrate that Exo@TDPs can cross the BBB, target GBM cells, penetrate into deep tumor parenchyma, and release the therapeutic cargos effectively. Synergistic delivery of TMZ and DOX by Exo@TDPs exerts therapeutic effects to suppress the tumor growth and prolong the survival time of orthotopic syngeneic mouse GBM models. These findings suggest that our developed Exo@TDPs loaded with chemotherapeutic drugs may bring new possibilities for the application of tumor cell-derived exosomes for brain tumor treatment.</description><identifier>ISSN: 1998-0124</identifier><identifier>EISSN: 1998-0000</identifier><identifier>DOI: 10.1007/s12274-023-5921-6</identifier><language>eng</language><publisher>Beijing: Tsinghua University Press</publisher><subject>Animal models ; Atomic/Molecular Structure and Spectra ; Biomedicine ; Biosafety ; Biotechnology ; Blood-brain barrier ; Brain cancer ; Brain tumors ; Chemistry and Materials Science ; Chemotherapy ; Condensed Matter Physics ; Doxorubicin ; Drug delivery ; Drug delivery systems ; Exosomes ; Glioblastoma ; Glioma cells ; In vivo methods and tests ; Materials Science ; Medical prognosis ; Nanotechnology ; Parenchyma ; Peptides ; Research Article ; Stem cells ; Temozolomide ; Tumor cells ; Tumors</subject><ispartof>Nano research, 2023-12, Vol.16 (12), p.13283-13293</ispartof><rights>Tsinghua University Press 2023</rights><rights>Tsinghua University Press 2023.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c316t-dde281ac54bcbfa6ed32ab665df897071cfc93fd2b9ffadc82d6bb332a09b6b3</citedby><cites>FETCH-LOGICAL-c316t-dde281ac54bcbfa6ed32ab665df897071cfc93fd2b9ffadc82d6bb332a09b6b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12274-023-5921-6$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12274-023-5921-6$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids></links><search><creatorcontrib>Zhou, Ying</creatorcontrib><creatorcontrib>Wang, Long</creatorcontrib><creatorcontrib>Chen, Lufei</creatorcontrib><creatorcontrib>Wu, Wei</creatorcontrib><creatorcontrib>Yang, Zhimin</creatorcontrib><creatorcontrib>Wang, Yuanzhuo</creatorcontrib><creatorcontrib>Wang, Anqi</creatorcontrib><creatorcontrib>Jiang, Sujun</creatorcontrib><creatorcontrib>Qin, Xuzhen</creatorcontrib><creatorcontrib>Ye, Zucheng</creatorcontrib><creatorcontrib>Hu, Zhiyuan</creatorcontrib><creatorcontrib>Wang, Zihua</creatorcontrib><title>Glioblastoma cell-derived exosomes functionalized with peptides as efficient nanocarriers for synergistic chemotherapy of glioblastoma with improved biosafety</title><title>Nano research</title><addtitle>Nano Res</addtitle><description>Glioblastoma (GBM) has been regarded as one of the most deadly and challenging cancers to treat with extremely poor prognosis. The limited efficacy of current chemotherapies might be attributed to the presence of glioma stem cells (GSCs) as well as the difficulties in passing through the blood–brain barrier (BBB) and targeting tumor cells. Tumor-derived exosomes are emerging as novel and promising drug delivery systems. However, great concerns regarding the biosafety and BBB penetrability remain to be addressed. Herein, we have developed a simple and feasible strategy to engineer GBM cell-derived exosomes with improved biosafety termed “Exo@TDPs” to deliver the cargos of chemotherapeutic agents temozolomide (TMZ) and doxorubicin (DOX) into GBM tissues. Exo@TDPs decorated with angiopep-2 (Ang-2) and CD133-targeted peptides improve the capacity to penetrate the BBB and target tumor cells. Both
in vitro
and
in vivo
studies demonstrate that Exo@TDPs can cross the BBB, target GBM cells, penetrate into deep tumor parenchyma, and release the therapeutic cargos effectively. Synergistic delivery of TMZ and DOX by Exo@TDPs exerts therapeutic effects to suppress the tumor growth and prolong the survival time of orthotopic syngeneic mouse GBM models. These findings suggest that our developed Exo@TDPs loaded with chemotherapeutic drugs may bring new possibilities for the application of tumor cell-derived exosomes for brain tumor treatment.</description><subject>Animal models</subject><subject>Atomic/Molecular Structure and Spectra</subject><subject>Biomedicine</subject><subject>Biosafety</subject><subject>Biotechnology</subject><subject>Blood-brain barrier</subject><subject>Brain cancer</subject><subject>Brain tumors</subject><subject>Chemistry and Materials Science</subject><subject>Chemotherapy</subject><subject>Condensed Matter Physics</subject><subject>Doxorubicin</subject><subject>Drug delivery</subject><subject>Drug delivery systems</subject><subject>Exosomes</subject><subject>Glioblastoma</subject><subject>Glioma cells</subject><subject>In vivo methods and tests</subject><subject>Materials Science</subject><subject>Medical prognosis</subject><subject>Nanotechnology</subject><subject>Parenchyma</subject><subject>Peptides</subject><subject>Research Article</subject><subject>Stem cells</subject><subject>Temozolomide</subject><subject>Tumor cells</subject><subject>Tumors</subject><issn>1998-0124</issn><issn>1998-0000</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp1UUtOwzAQjRBIlMIB2FliHbCd1kmWqIKCVIlN95Y_49ZVEgfbBcJhOCsuAcGG2cxo5n00ell2SfA1wbi8CYTScpZjWuTzmpKcHWUTUtdVjlMd_8yEzk6zsxB2GDNKZtUk-1g21slGhOhagRQ0Ta7B2xfQCN5ccC0EZPaditZ1orHvaf9q4xb10Eer01EEBMZYZaGLqBOdU8J7Cz7RnEdh6MBvbIhWIbWF1sUteNEPyBm0-ev8JWrb3ruDtbQuCANxOM9OjGgCXHz3aba-v1svHvLV0_JxcbvKVUFYzLUGWhGh5jOppBEMdEGFZGyuTVWXuCTKqLowmsraGKFVRTWTskggXEsmi2l2Ncom_-c9hMh3bu_Tw4HTGicJNi9IQpERpbwLwYPhvbet8AMnmB9S4GMKPKXADylwljh05ISE7Tbgf5X_J30CIaWRYw</recordid><startdate>20231201</startdate><enddate>20231201</enddate><creator>Zhou, Ying</creator><creator>Wang, Long</creator><creator>Chen, Lufei</creator><creator>Wu, Wei</creator><creator>Yang, Zhimin</creator><creator>Wang, Yuanzhuo</creator><creator>Wang, Anqi</creator><creator>Jiang, Sujun</creator><creator>Qin, Xuzhen</creator><creator>Ye, Zucheng</creator><creator>Hu, Zhiyuan</creator><creator>Wang, Zihua</creator><general>Tsinghua University Press</general><general>Springer Nature B.V</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QF</scope><scope>7QO</scope><scope>7QQ</scope><scope>7SE</scope><scope>7SR</scope><scope>7U5</scope><scope>7X7</scope><scope>7XB</scope><scope>8AO</scope><scope>8BQ</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H8G</scope><scope>HCIFZ</scope><scope>JG9</scope><scope>K9.</scope><scope>KB.</scope><scope>L7M</scope><scope>LK8</scope><scope>M0S</scope><scope>M7P</scope><scope>P64</scope><scope>PDBOC</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope></search><sort><creationdate>20231201</creationdate><title>Glioblastoma cell-derived exosomes functionalized with peptides as efficient nanocarriers for synergistic chemotherapy of glioblastoma with improved biosafety</title><author>Zhou, Ying ; Wang, Long ; Chen, Lufei ; Wu, Wei ; Yang, Zhimin ; Wang, Yuanzhuo ; Wang, Anqi ; Jiang, Sujun ; Qin, Xuzhen ; Ye, Zucheng ; Hu, Zhiyuan ; Wang, Zihua</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c316t-dde281ac54bcbfa6ed32ab665df897071cfc93fd2b9ffadc82d6bb332a09b6b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Animal models</topic><topic>Atomic/Molecular Structure and Spectra</topic><topic>Biomedicine</topic><topic>Biosafety</topic><topic>Biotechnology</topic><topic>Blood-brain barrier</topic><topic>Brain cancer</topic><topic>Brain tumors</topic><topic>Chemistry and Materials Science</topic><topic>Chemotherapy</topic><topic>Condensed Matter Physics</topic><topic>Doxorubicin</topic><topic>Drug delivery</topic><topic>Drug delivery systems</topic><topic>Exosomes</topic><topic>Glioblastoma</topic><topic>Glioma cells</topic><topic>In vivo methods and tests</topic><topic>Materials Science</topic><topic>Medical prognosis</topic><topic>Nanotechnology</topic><topic>Parenchyma</topic><topic>Peptides</topic><topic>Research Article</topic><topic>Stem cells</topic><topic>Temozolomide</topic><topic>Tumor cells</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhou, Ying</creatorcontrib><creatorcontrib>Wang, Long</creatorcontrib><creatorcontrib>Chen, Lufei</creatorcontrib><creatorcontrib>Wu, Wei</creatorcontrib><creatorcontrib>Yang, Zhimin</creatorcontrib><creatorcontrib>Wang, Yuanzhuo</creatorcontrib><creatorcontrib>Wang, Anqi</creatorcontrib><creatorcontrib>Jiang, Sujun</creatorcontrib><creatorcontrib>Qin, Xuzhen</creatorcontrib><creatorcontrib>Ye, Zucheng</creatorcontrib><creatorcontrib>Hu, Zhiyuan</creatorcontrib><creatorcontrib>Wang, Zihua</creatorcontrib><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Aluminium Industry Abstracts</collection><collection>Biotechnology Research Abstracts</collection><collection>Ceramic Abstracts</collection><collection>Corrosion Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest Pharma Collection</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</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>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Copper Technical Reference Library</collection><collection>SciTech Premium Collection</collection><collection>Materials Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Materials Science Collection</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><jtitle>Nano research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhou, Ying</au><au>Wang, Long</au><au>Chen, Lufei</au><au>Wu, Wei</au><au>Yang, Zhimin</au><au>Wang, Yuanzhuo</au><au>Wang, Anqi</au><au>Jiang, Sujun</au><au>Qin, Xuzhen</au><au>Ye, Zucheng</au><au>Hu, Zhiyuan</au><au>Wang, Zihua</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Glioblastoma cell-derived exosomes functionalized with peptides as efficient nanocarriers for synergistic chemotherapy of glioblastoma with improved biosafety</atitle><jtitle>Nano research</jtitle><stitle>Nano Res</stitle><date>2023-12-01</date><risdate>2023</risdate><volume>16</volume><issue>12</issue><spage>13283</spage><epage>13293</epage><pages>13283-13293</pages><issn>1998-0124</issn><eissn>1998-0000</eissn><abstract>Glioblastoma (GBM) has been regarded as one of the most deadly and challenging cancers to treat with extremely poor prognosis. The limited efficacy of current chemotherapies might be attributed to the presence of glioma stem cells (GSCs) as well as the difficulties in passing through the blood–brain barrier (BBB) and targeting tumor cells. Tumor-derived exosomes are emerging as novel and promising drug delivery systems. However, great concerns regarding the biosafety and BBB penetrability remain to be addressed. Herein, we have developed a simple and feasible strategy to engineer GBM cell-derived exosomes with improved biosafety termed “Exo@TDPs” to deliver the cargos of chemotherapeutic agents temozolomide (TMZ) and doxorubicin (DOX) into GBM tissues. Exo@TDPs decorated with angiopep-2 (Ang-2) and CD133-targeted peptides improve the capacity to penetrate the BBB and target tumor cells. Both
in vitro
and
in vivo
studies demonstrate that Exo@TDPs can cross the BBB, target GBM cells, penetrate into deep tumor parenchyma, and release the therapeutic cargos effectively. Synergistic delivery of TMZ and DOX by Exo@TDPs exerts therapeutic effects to suppress the tumor growth and prolong the survival time of orthotopic syngeneic mouse GBM models. These findings suggest that our developed Exo@TDPs loaded with chemotherapeutic drugs may bring new possibilities for the application of tumor cell-derived exosomes for brain tumor treatment.</abstract><cop>Beijing</cop><pub>Tsinghua University Press</pub><doi>10.1007/s12274-023-5921-6</doi><tpages>11</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1998-0124 |
| ispartof | Nano research, 2023-12, Vol.16 (12), p.13283-13293 |
| issn | 1998-0124 1998-0000 |
| language | eng |
| recordid | cdi_proquest_journals_2908976531 |
| source | SpringerLink Journals - AutoHoldings |
| subjects | Animal models Atomic/Molecular Structure and Spectra Biomedicine Biosafety Biotechnology Blood-brain barrier Brain cancer Brain tumors Chemistry and Materials Science Chemotherapy Condensed Matter Physics Doxorubicin Drug delivery Drug delivery systems Exosomes Glioblastoma Glioma cells In vivo methods and tests Materials Science Medical prognosis Nanotechnology Parenchyma Peptides Research Article Stem cells Temozolomide Tumor cells Tumors |
| title | Glioblastoma cell-derived exosomes functionalized with peptides as efficient nanocarriers for synergistic chemotherapy of glioblastoma with improved biosafety |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T00%3A41%3A28IST&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=Glioblastoma%20cell-derived%20exosomes%20functionalized%20with%20peptides%20as%20efficient%20nanocarriers%20for%20synergistic%20chemotherapy%20of%20glioblastoma%20with%20improved%20biosafety&rft.jtitle=Nano%20research&rft.au=Zhou,%20Ying&rft.date=2023-12-01&rft.volume=16&rft.issue=12&rft.spage=13283&rft.epage=13293&rft.pages=13283-13293&rft.issn=1998-0124&rft.eissn=1998-0000&rft_id=info:doi/10.1007/s12274-023-5921-6&rft_dat=%3Cproquest_cross%3E2908976531%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=2908976531&rft_id=info:pmid/&rfr_iscdi=true |