Nanofunctionalized Microparticles for Glucose Delivery in Three-Dimensional Cell Assemblies
Three-dimensional (3D) cell assemblies, such as multicellular spheroids, can be powerful biological tools to closely mimic the complexity of cell–cell and cell–matrix interactions in a native-like microenvironment. However, potential applications of large spheroids are limited by the insufficient di...
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creator | Fois, Maria G. Zengin, Aygul Song, Ke Giselbrecht, Stefan Habibović, Pamela Truckenmüller, Roman K. van Rijt, Sabine Tahmasebi Birgani, Zeinab N. |
description | Three-dimensional (3D) cell assemblies, such as multicellular spheroids, can be powerful biological tools to closely mimic the complexity of cell–cell and cell–matrix interactions in a native-like microenvironment. However, potential applications of large spheroids are limited by the insufficient diffusion of oxygen and nutrients through the spheroids and, thus, result in the formation of a necrotic core. To overcome this drawback, we present a new strategy based on nanoparticle-coated microparticles. In this study, microparticles function as synthetic centers to regulate the diffusion of small molecules, such as oxygen and nutrients, within human mesenchymal stem cell (hMSC) spheroids. The nanoparticle coating on the microparticle surface acts as a nutrient reservoir to release glucose locally within the spheroids. We first coated the surface of the poly(lactic-co-glycolic acid) (PLGA) microparticles with mesoporous silica nanoparticles (MSNs) based on electrostatic interactions and then formed cell-nanofunctionalized microparticle spheroids. Next, we investigated the stability of the MSN coating on the microparticles’ surface during 14 days of incubation in cell culture medium at 37 °C. Then, we evaluated the influence of MSN-coated PLGA microparticles on spheroid aggregation and cell viability. Our results showed the formation of homogeneous spheroids with good cell viability. As a proof of concept, fluorescently labeled glucose (2-NBD glucose) was loaded into the MSNs at different concentrations, and the release behavior was monitored. For cell culture studies, glucose was loaded into the MSNs coated onto the PLGA microparticles to sustain local nutrient release within the hMSC spheroids. In vitro results demonstrated that the local delivery of glucose from MSNs enhanced the cell viability in spheroids during a short-term hypoxic culture. Taken together, the newly developed nanofunctionalized microparticle-based delivery system may offer a versatile platform for local delivery of small molecules within 3D cellular assemblies and, thus, improve cell viability in spheroids. |
doi_str_mv | 10.1021/acsami.4c02321 |
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However, potential applications of large spheroids are limited by the insufficient diffusion of oxygen and nutrients through the spheroids and, thus, result in the formation of a necrotic core. To overcome this drawback, we present a new strategy based on nanoparticle-coated microparticles. In this study, microparticles function as synthetic centers to regulate the diffusion of small molecules, such as oxygen and nutrients, within human mesenchymal stem cell (hMSC) spheroids. The nanoparticle coating on the microparticle surface acts as a nutrient reservoir to release glucose locally within the spheroids. We first coated the surface of the poly(lactic-co-glycolic acid) (PLGA) microparticles with mesoporous silica nanoparticles (MSNs) based on electrostatic interactions and then formed cell-nanofunctionalized microparticle spheroids. Next, we investigated the stability of the MSN coating on the microparticles’ surface during 14 days of incubation in cell culture medium at 37 °C. Then, we evaluated the influence of MSN-coated PLGA microparticles on spheroid aggregation and cell viability. Our results showed the formation of homogeneous spheroids with good cell viability. As a proof of concept, fluorescently labeled glucose (2-NBD glucose) was loaded into the MSNs at different concentrations, and the release behavior was monitored. For cell culture studies, glucose was loaded into the MSNs coated onto the PLGA microparticles to sustain local nutrient release within the hMSC spheroids. In vitro results demonstrated that the local delivery of glucose from MSNs enhanced the cell viability in spheroids during a short-term hypoxic culture. Taken together, the newly developed nanofunctionalized microparticle-based delivery system may offer a versatile platform for local delivery of small molecules within 3D cellular assemblies and, thus, improve cell viability in spheroids.</description><identifier>ISSN: 1944-8244</identifier><identifier>ISSN: 1944-8252</identifier><identifier>EISSN: 1944-8252</identifier><identifier>DOI: 10.1021/acsami.4c02321</identifier><identifier>PMID: 38561903</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Biological and Medical Applications of Materials and Interfaces ; cell culture ; cell viability ; culture media ; glucose ; humans ; mesenchymal stromal cells ; microparticles ; nanoparticles ; oxygen ; porous media ; silica</subject><ispartof>ACS applied materials & interfaces, 2024-04, Vol.16 (14), p.17347-17360</ispartof><rights>2024 The Authors. Published by American Chemical Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-a358t-23ecdf76a5cf072b401360c68a482fca6cf36b00cb9490949cd6f8daf91bee7d3</cites><orcidid>0000-0001-7541-525X ; 0000-0002-7866-2499 ; 0000-0001-9304-1554 ; 0000-0003-4102-4626 ; 0000-0002-1354-0167 ; 0000-0002-7105-1636 ; 0000-0003-3899-922X ; 0000-0001-8249-5155</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/acsami.4c02321$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/acsami.4c02321$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,776,780,2752,27053,27901,27902,56713,56763</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38561903$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fois, Maria G.</creatorcontrib><creatorcontrib>Zengin, Aygul</creatorcontrib><creatorcontrib>Song, Ke</creatorcontrib><creatorcontrib>Giselbrecht, Stefan</creatorcontrib><creatorcontrib>Habibović, Pamela</creatorcontrib><creatorcontrib>Truckenmüller, Roman K.</creatorcontrib><creatorcontrib>van Rijt, Sabine</creatorcontrib><creatorcontrib>Tahmasebi Birgani, Zeinab N.</creatorcontrib><title>Nanofunctionalized Microparticles for Glucose Delivery in Three-Dimensional Cell Assemblies</title><title>ACS applied materials & interfaces</title><addtitle>ACS Appl. Mater. Interfaces</addtitle><description>Three-dimensional (3D) cell assemblies, such as multicellular spheroids, can be powerful biological tools to closely mimic the complexity of cell–cell and cell–matrix interactions in a native-like microenvironment. However, potential applications of large spheroids are limited by the insufficient diffusion of oxygen and nutrients through the spheroids and, thus, result in the formation of a necrotic core. To overcome this drawback, we present a new strategy based on nanoparticle-coated microparticles. In this study, microparticles function as synthetic centers to regulate the diffusion of small molecules, such as oxygen and nutrients, within human mesenchymal stem cell (hMSC) spheroids. The nanoparticle coating on the microparticle surface acts as a nutrient reservoir to release glucose locally within the spheroids. We first coated the surface of the poly(lactic-co-glycolic acid) (PLGA) microparticles with mesoporous silica nanoparticles (MSNs) based on electrostatic interactions and then formed cell-nanofunctionalized microparticle spheroids. Next, we investigated the stability of the MSN coating on the microparticles’ surface during 14 days of incubation in cell culture medium at 37 °C. Then, we evaluated the influence of MSN-coated PLGA microparticles on spheroid aggregation and cell viability. Our results showed the formation of homogeneous spheroids with good cell viability. As a proof of concept, fluorescently labeled glucose (2-NBD glucose) was loaded into the MSNs at different concentrations, and the release behavior was monitored. For cell culture studies, glucose was loaded into the MSNs coated onto the PLGA microparticles to sustain local nutrient release within the hMSC spheroids. In vitro results demonstrated that the local delivery of glucose from MSNs enhanced the cell viability in spheroids during a short-term hypoxic culture. Taken together, the newly developed nanofunctionalized microparticle-based delivery system may offer a versatile platform for local delivery of small molecules within 3D cellular assemblies and, thus, improve cell viability in spheroids.</description><subject>Biological and Medical Applications of Materials and Interfaces</subject><subject>cell culture</subject><subject>cell viability</subject><subject>culture media</subject><subject>glucose</subject><subject>humans</subject><subject>mesenchymal stromal cells</subject><subject>microparticles</subject><subject>nanoparticles</subject><subject>oxygen</subject><subject>porous media</subject><subject>silica</subject><issn>1944-8244</issn><issn>1944-8252</issn><issn>1944-8252</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNqFkDtPwzAURi0EoqWwMiKPCCnFryTOWLVQkHgsZWKIHOdauMqj2AlS-fUYUrohhqt7h_N9ujoInVMypYTRa6W9qu1UaMI4owdoTDMhIslidri_hRihE-_XhCSckfgYjbiME5oRPkavT6ppTd_ozraNquwnlPjRatdulOusrsBj0zq8rHrdesALqOwHuC22DV69OYBoYWto_E8Yz6Gq8Mx7qIvKgj9FR0ZVHs52e4Jebm9W87vo4Xl5P589RIrHsosYB12aNFGxNiRlhSCUJ0QnUgnJjFaJNjwpCNFFJjISRpeJkaUyGS0A0pJP0OXQu3Htew--y2vrdfhFNdD2Puc05jSVmeT_o4RTGniRBnQ6oEGG9w5MvnG2Vm6bU5J_u88H9_nOfQhc7Lr7ooZyj__KDsDVAIRgvm57F5z5v9q-AIf3j5s</recordid><startdate>20240410</startdate><enddate>20240410</enddate><creator>Fois, Maria G.</creator><creator>Zengin, Aygul</creator><creator>Song, Ke</creator><creator>Giselbrecht, Stefan</creator><creator>Habibović, Pamela</creator><creator>Truckenmüller, Roman K.</creator><creator>van Rijt, Sabine</creator><creator>Tahmasebi Birgani, Zeinab N.</creator><general>American Chemical Society</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7S9</scope><scope>L.6</scope><orcidid>https://orcid.org/0000-0001-7541-525X</orcidid><orcidid>https://orcid.org/0000-0002-7866-2499</orcidid><orcidid>https://orcid.org/0000-0001-9304-1554</orcidid><orcidid>https://orcid.org/0000-0003-4102-4626</orcidid><orcidid>https://orcid.org/0000-0002-1354-0167</orcidid><orcidid>https://orcid.org/0000-0002-7105-1636</orcidid><orcidid>https://orcid.org/0000-0003-3899-922X</orcidid><orcidid>https://orcid.org/0000-0001-8249-5155</orcidid></search><sort><creationdate>20240410</creationdate><title>Nanofunctionalized Microparticles for Glucose Delivery in Three-Dimensional Cell Assemblies</title><author>Fois, Maria G. ; Zengin, Aygul ; Song, Ke ; Giselbrecht, Stefan ; Habibović, Pamela ; Truckenmüller, Roman K. ; van Rijt, Sabine ; Tahmasebi Birgani, Zeinab N.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a358t-23ecdf76a5cf072b401360c68a482fca6cf36b00cb9490949cd6f8daf91bee7d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Biological and Medical Applications of Materials and Interfaces</topic><topic>cell culture</topic><topic>cell viability</topic><topic>culture media</topic><topic>glucose</topic><topic>humans</topic><topic>mesenchymal stromal cells</topic><topic>microparticles</topic><topic>nanoparticles</topic><topic>oxygen</topic><topic>porous media</topic><topic>silica</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fois, Maria G.</creatorcontrib><creatorcontrib>Zengin, Aygul</creatorcontrib><creatorcontrib>Song, Ke</creatorcontrib><creatorcontrib>Giselbrecht, Stefan</creatorcontrib><creatorcontrib>Habibović, Pamela</creatorcontrib><creatorcontrib>Truckenmüller, Roman K.</creatorcontrib><creatorcontrib>van Rijt, Sabine</creatorcontrib><creatorcontrib>Tahmasebi Birgani, Zeinab N.</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><jtitle>ACS applied materials & interfaces</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fois, Maria G.</au><au>Zengin, Aygul</au><au>Song, Ke</au><au>Giselbrecht, Stefan</au><au>Habibović, Pamela</au><au>Truckenmüller, Roman K.</au><au>van Rijt, Sabine</au><au>Tahmasebi Birgani, Zeinab N.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Nanofunctionalized Microparticles for Glucose Delivery in Three-Dimensional Cell Assemblies</atitle><jtitle>ACS applied materials & interfaces</jtitle><addtitle>ACS Appl. Mater. Interfaces</addtitle><date>2024-04-10</date><risdate>2024</risdate><volume>16</volume><issue>14</issue><spage>17347</spage><epage>17360</epage><pages>17347-17360</pages><issn>1944-8244</issn><issn>1944-8252</issn><eissn>1944-8252</eissn><abstract>Three-dimensional (3D) cell assemblies, such as multicellular spheroids, can be powerful biological tools to closely mimic the complexity of cell–cell and cell–matrix interactions in a native-like microenvironment. However, potential applications of large spheroids are limited by the insufficient diffusion of oxygen and nutrients through the spheroids and, thus, result in the formation of a necrotic core. To overcome this drawback, we present a new strategy based on nanoparticle-coated microparticles. In this study, microparticles function as synthetic centers to regulate the diffusion of small molecules, such as oxygen and nutrients, within human mesenchymal stem cell (hMSC) spheroids. The nanoparticle coating on the microparticle surface acts as a nutrient reservoir to release glucose locally within the spheroids. We first coated the surface of the poly(lactic-co-glycolic acid) (PLGA) microparticles with mesoporous silica nanoparticles (MSNs) based on electrostatic interactions and then formed cell-nanofunctionalized microparticle spheroids. Next, we investigated the stability of the MSN coating on the microparticles’ surface during 14 days of incubation in cell culture medium at 37 °C. Then, we evaluated the influence of MSN-coated PLGA microparticles on spheroid aggregation and cell viability. Our results showed the formation of homogeneous spheroids with good cell viability. As a proof of concept, fluorescently labeled glucose (2-NBD glucose) was loaded into the MSNs at different concentrations, and the release behavior was monitored. For cell culture studies, glucose was loaded into the MSNs coated onto the PLGA microparticles to sustain local nutrient release within the hMSC spheroids. In vitro results demonstrated that the local delivery of glucose from MSNs enhanced the cell viability in spheroids during a short-term hypoxic culture. Taken together, the newly developed nanofunctionalized microparticle-based delivery system may offer a versatile platform for local delivery of small molecules within 3D cellular assemblies and, thus, improve cell viability in spheroids.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>38561903</pmid><doi>10.1021/acsami.4c02321</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0001-7541-525X</orcidid><orcidid>https://orcid.org/0000-0002-7866-2499</orcidid><orcidid>https://orcid.org/0000-0001-9304-1554</orcidid><orcidid>https://orcid.org/0000-0003-4102-4626</orcidid><orcidid>https://orcid.org/0000-0002-1354-0167</orcidid><orcidid>https://orcid.org/0000-0002-7105-1636</orcidid><orcidid>https://orcid.org/0000-0003-3899-922X</orcidid><orcidid>https://orcid.org/0000-0001-8249-5155</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Biological and Medical Applications of Materials and Interfaces cell culture cell viability culture media glucose humans mesenchymal stromal cells microparticles nanoparticles oxygen porous media silica |
title | Nanofunctionalized Microparticles for Glucose Delivery in Three-Dimensional Cell Assemblies |
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