A Microfluidic 3D‐Tumor‐Spheroid Model for the Evaluation of Targeted Therapies from Angiogenesis‐Related Cytokines at the Single Spheroid Level
Angiogenesis is a key player in drug resistance to targeted therapies for breast cancer. The average expression of angiogenesis‐related cytokines is widely associated with the treatments of target therapies for a population of cells or spheroids, overlooking the distinct responses for individuals. I...
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description | Angiogenesis is a key player in drug resistance to targeted therapies for breast cancer. The average expression of angiogenesis‐related cytokines is widely associated with the treatments of target therapies for a population of cells or spheroids, overlooking the distinct responses for individuals. In this work, a highly integrated microfluidic platform is developed for the generation of monodisperse multicellular tumor spheroids (MTSs), drug treatments, and the measurement of cytokines for individual MTSs in a single chip. The platform allows the correlation evaluation between cytokine secretion and drug treatment at the level of individual spheroids. For validation, quantities of six representative proangiogenic cytokines are tested against treatments with four model drugs at varying times and concentrations. By applying a linear regression model, significant correlations are established between cytokine secretion and the treated drug concentration for individual spheroids. The proposed platform provides a high‐throughput method for the investigation of the molecular mechanism of the cytokine response to targeted therapies and paves the way for future drug screening using predictive regression models at the single‐spheroid level.
In this work, a microfluidic platform is provided that allows for the integration of multiple functions within a single microfluidic chip. These include monodisperse multicellular tumor spheroids (MTS) generation, drug treatment, and cytokine detection. From this platform, the correlation between angiogenesis‐related cytokines and the treated drug concentration can be established at the single spheroid level. |
doi_str_mv | 10.1002/adhm.202402321 |
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In this work, a microfluidic platform is provided that allows for the integration of multiple functions within a single microfluidic chip. These include monodisperse multicellular tumor spheroids (MTS) generation, drug treatment, and cytokine detection. From this platform, the correlation between angiogenesis‐related cytokines and the treated drug concentration can be established at the single spheroid level.</description><identifier>ISSN: 2192-2640</identifier><identifier>ISSN: 2192-2659</identifier><identifier>EISSN: 2192-2659</identifier><identifier>DOI: 10.1002/adhm.202402321</identifier><identifier>PMID: 39126126</identifier><language>eng</language><publisher>Germany: Wiley Subscription Services, Inc</publisher><subject>Angiogenesis ; angiogenesis‐related cytokines ; Breast cancer ; Breast Neoplasms - drug therapy ; Breast Neoplasms - metabolism ; Breast Neoplasms - pathology ; Cell Line, Tumor ; Cytokines ; Cytokines - metabolism ; Drug development ; Drug resistance ; Drug screening ; Female ; Humans ; linear regression models ; microfluidic platform ; Microfluidics ; Microfluidics - methods ; Molecular modelling ; Multicellular tumor spheroids ; Neovascularization, Pathologic - drug therapy ; Neovascularization, Pathologic - metabolism ; Regression analysis ; Regression models ; single spheroids ; Spheroids ; Spheroids, Cellular - drug effects ; Spheroids, Cellular - metabolism ; targeted drugs ; Tumors</subject><ispartof>Advanced healthcare materials, 2024-12, Vol.13 (31), p.e2402321-n/a</ispartof><rights>2024 Wiley‐VCH GmbH</rights><rights>2024 Wiley‐VCH GmbH.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c2581-fcdab185268e5067cc2fc065460795a4f10a62d2086db140441f5d12f497f6103</cites><orcidid>0000-0003-0461-2031</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fadhm.202402321$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fadhm.202402321$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39126126$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liu, Mengqi</creatorcontrib><creatorcontrib>Wang, Yihe</creatorcontrib><creatorcontrib>Wang, Chao</creatorcontrib><creatorcontrib>Li, Ping</creatorcontrib><creatorcontrib>Qiu, Jiaoyan</creatorcontrib><creatorcontrib>Yang, Ningkai</creatorcontrib><creatorcontrib>Sun, Mingyuan</creatorcontrib><creatorcontrib>Han, Lin</creatorcontrib><title>A Microfluidic 3D‐Tumor‐Spheroid Model for the Evaluation of Targeted Therapies from Angiogenesis‐Related Cytokines at the Single Spheroid Level</title><title>Advanced healthcare materials</title><addtitle>Adv Healthc Mater</addtitle><description>Angiogenesis is a key player in drug resistance to targeted therapies for breast cancer. The average expression of angiogenesis‐related cytokines is widely associated with the treatments of target therapies for a population of cells or spheroids, overlooking the distinct responses for individuals. In this work, a highly integrated microfluidic platform is developed for the generation of monodisperse multicellular tumor spheroids (MTSs), drug treatments, and the measurement of cytokines for individual MTSs in a single chip. The platform allows the correlation evaluation between cytokine secretion and drug treatment at the level of individual spheroids. For validation, quantities of six representative proangiogenic cytokines are tested against treatments with four model drugs at varying times and concentrations. By applying a linear regression model, significant correlations are established between cytokine secretion and the treated drug concentration for individual spheroids. The proposed platform provides a high‐throughput method for the investigation of the molecular mechanism of the cytokine response to targeted therapies and paves the way for future drug screening using predictive regression models at the single‐spheroid level.
In this work, a microfluidic platform is provided that allows for the integration of multiple functions within a single microfluidic chip. These include monodisperse multicellular tumor spheroids (MTS) generation, drug treatment, and cytokine detection. From this platform, the correlation between angiogenesis‐related cytokines and the treated drug concentration can be established at the single spheroid level.</description><subject>Angiogenesis</subject><subject>angiogenesis‐related cytokines</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - drug therapy</subject><subject>Breast Neoplasms - metabolism</subject><subject>Breast Neoplasms - pathology</subject><subject>Cell Line, Tumor</subject><subject>Cytokines</subject><subject>Cytokines - metabolism</subject><subject>Drug development</subject><subject>Drug resistance</subject><subject>Drug screening</subject><subject>Female</subject><subject>Humans</subject><subject>linear regression models</subject><subject>microfluidic platform</subject><subject>Microfluidics</subject><subject>Microfluidics - methods</subject><subject>Molecular modelling</subject><subject>Multicellular tumor spheroids</subject><subject>Neovascularization, Pathologic - drug therapy</subject><subject>Neovascularization, Pathologic - metabolism</subject><subject>Regression analysis</subject><subject>Regression models</subject><subject>single spheroids</subject><subject>Spheroids</subject><subject>Spheroids, Cellular - drug effects</subject><subject>Spheroids, Cellular - metabolism</subject><subject>targeted drugs</subject><subject>Tumors</subject><issn>2192-2640</issn><issn>2192-2659</issn><issn>2192-2659</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUFv2yAYhtG0qa26XHuckHbZJSlgjO1jlHZrpUSV2vSMiPlI6LDJwO6U235CT_2B-yUjTZNJvRQhfQg9PMD3InRGyYgSws6VXjUjRhgnLGP0AzphtGJDJvLq42HNyTEaxPhA0hA5FSU9QsdZRZlI8wQ9j_HM1sEb11tta5xd_P3zNO8bH1K9W68geKvxzGtw2PiAuxXgy0fletVZ32Jv8FyFJXSg8TzBam0hYhN8g8ft0voltBBtTK5bcGpLTTad_2nTLlbdi-3OtkuXyv6uKTyC-4w-GeUiDF7rKbr_fjmfXA2nNz-uJ-PpsGZ5SYem1mpBy5yJEnIiirpmpk7f5IIUVa64oUQJphkphV5QTjinJteUGV4VRlCSnaJvO-86-F89xE42NtbgnGrB91FmJHWqLIqsSOjXN-iD70ObXiczyvOsJBXfUqMdlXoaYwAj18E2KmwkJXIbmtyGJg-hpQNfXrX9ogF9wPcRJaDaAb-tg807Ojm-uJr9l_8DNjKlxg</recordid><startdate>202412</startdate><enddate>202412</enddate><creator>Liu, Mengqi</creator><creator>Wang, Yihe</creator><creator>Wang, Chao</creator><creator>Li, Ping</creator><creator>Qiu, Jiaoyan</creator><creator>Yang, Ningkai</creator><creator>Sun, Mingyuan</creator><creator>Han, Lin</creator><general>Wiley Subscription Services, Inc</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>7QF</scope><scope>7QP</scope><scope>7QQ</scope><scope>7SC</scope><scope>7SE</scope><scope>7SP</scope><scope>7SR</scope><scope>7T5</scope><scope>7TA</scope><scope>7TB</scope><scope>7TM</scope><scope>7TO</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>H94</scope><scope>JG9</scope><scope>JQ2</scope><scope>K9.</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-0461-2031</orcidid></search><sort><creationdate>202412</creationdate><title>A Microfluidic 3D‐Tumor‐Spheroid Model for the Evaluation of Targeted Therapies from Angiogenesis‐Related Cytokines at the Single Spheroid Level</title><author>Liu, Mengqi ; Wang, Yihe ; Wang, Chao ; Li, Ping ; Qiu, Jiaoyan ; Yang, Ningkai ; Sun, Mingyuan ; Han, Lin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2581-fcdab185268e5067cc2fc065460795a4f10a62d2086db140441f5d12f497f6103</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Angiogenesis</topic><topic>angiogenesis‐related cytokines</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - drug therapy</topic><topic>Breast Neoplasms - metabolism</topic><topic>Breast Neoplasms - pathology</topic><topic>Cell Line, Tumor</topic><topic>Cytokines</topic><topic>Cytokines - metabolism</topic><topic>Drug development</topic><topic>Drug resistance</topic><topic>Drug screening</topic><topic>Female</topic><topic>Humans</topic><topic>linear regression models</topic><topic>microfluidic platform</topic><topic>Microfluidics</topic><topic>Microfluidics - methods</topic><topic>Molecular modelling</topic><topic>Multicellular tumor spheroids</topic><topic>Neovascularization, Pathologic - drug therapy</topic><topic>Neovascularization, Pathologic - metabolism</topic><topic>Regression analysis</topic><topic>Regression models</topic><topic>single spheroids</topic><topic>Spheroids</topic><topic>Spheroids, Cellular - drug effects</topic><topic>Spheroids, Cellular - metabolism</topic><topic>targeted drugs</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liu, Mengqi</creatorcontrib><creatorcontrib>Wang, Yihe</creatorcontrib><creatorcontrib>Wang, Chao</creatorcontrib><creatorcontrib>Li, Ping</creatorcontrib><creatorcontrib>Qiu, Jiaoyan</creatorcontrib><creatorcontrib>Yang, Ningkai</creatorcontrib><creatorcontrib>Sun, Mingyuan</creatorcontrib><creatorcontrib>Han, Lin</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Aluminium Industry Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Ceramic Abstracts</collection><collection>Computer and Information Systems Abstracts</collection><collection>Corrosion Abstracts</collection><collection>Electronics & Communications Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Immunology Abstracts</collection><collection>Materials Business File</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Engineering Research Database</collection><collection>Aerospace Database</collection><collection>Copper Technical Reference Library</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Materials Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Civil Engineering Abstracts</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>Computer and Information Systems Abstracts Academic</collection><collection>Computer and Information Systems Abstracts Professional</collection><collection>MEDLINE - Academic</collection><jtitle>Advanced healthcare materials</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, Mengqi</au><au>Wang, Yihe</au><au>Wang, Chao</au><au>Li, Ping</au><au>Qiu, Jiaoyan</au><au>Yang, Ningkai</au><au>Sun, Mingyuan</au><au>Han, Lin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Microfluidic 3D‐Tumor‐Spheroid Model for the Evaluation of Targeted Therapies from Angiogenesis‐Related Cytokines at the Single Spheroid Level</atitle><jtitle>Advanced healthcare materials</jtitle><addtitle>Adv Healthc Mater</addtitle><date>2024-12</date><risdate>2024</risdate><volume>13</volume><issue>31</issue><spage>e2402321</spage><epage>n/a</epage><pages>e2402321-n/a</pages><issn>2192-2640</issn><issn>2192-2659</issn><eissn>2192-2659</eissn><abstract>Angiogenesis is a key player in drug resistance to targeted therapies for breast cancer. The average expression of angiogenesis‐related cytokines is widely associated with the treatments of target therapies for a population of cells or spheroids, overlooking the distinct responses for individuals. In this work, a highly integrated microfluidic platform is developed for the generation of monodisperse multicellular tumor spheroids (MTSs), drug treatments, and the measurement of cytokines for individual MTSs in a single chip. The platform allows the correlation evaluation between cytokine secretion and drug treatment at the level of individual spheroids. For validation, quantities of six representative proangiogenic cytokines are tested against treatments with four model drugs at varying times and concentrations. By applying a linear regression model, significant correlations are established between cytokine secretion and the treated drug concentration for individual spheroids. The proposed platform provides a high‐throughput method for the investigation of the molecular mechanism of the cytokine response to targeted therapies and paves the way for future drug screening using predictive regression models at the single‐spheroid level.
In this work, a microfluidic platform is provided that allows for the integration of multiple functions within a single microfluidic chip. These include monodisperse multicellular tumor spheroids (MTS) generation, drug treatment, and cytokine detection. From this platform, the correlation between angiogenesis‐related cytokines and the treated drug concentration can be established at the single spheroid level.</abstract><cop>Germany</cop><pub>Wiley Subscription Services, Inc</pub><pmid>39126126</pmid><doi>10.1002/adhm.202402321</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0003-0461-2031</orcidid></addata></record> |
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subjects | Angiogenesis angiogenesis‐related cytokines Breast cancer Breast Neoplasms - drug therapy Breast Neoplasms - metabolism Breast Neoplasms - pathology Cell Line, Tumor Cytokines Cytokines - metabolism Drug development Drug resistance Drug screening Female Humans linear regression models microfluidic platform Microfluidics Microfluidics - methods Molecular modelling Multicellular tumor spheroids Neovascularization, Pathologic - drug therapy Neovascularization, Pathologic - metabolism Regression analysis Regression models single spheroids Spheroids Spheroids, Cellular - drug effects Spheroids, Cellular - metabolism targeted drugs Tumors |
title | A Microfluidic 3D‐Tumor‐Spheroid Model for the Evaluation of Targeted Therapies from Angiogenesis‐Related Cytokines at the Single Spheroid Level |
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