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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Veröffentlicht in:ACS applied materials & interfaces 2024-04, Vol.16 (14), p.17347-17360
Hauptverfasser: Fois, Maria G., Zengin, Aygul, Song, Ke, Giselbrecht, Stefan, Habibović, Pamela, Truckenmüller, Roman K., van Rijt, Sabine, Tahmasebi Birgani, Zeinab N.
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container_end_page 17360
container_issue 14
container_start_page 17347
container_title ACS applied materials & interfaces
container_volume 16
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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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. 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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. 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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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