Implementation of a Dynamic Co-Culture Model Abated Silver Nanoparticle Interactions and Nanotoxicological Outcomes In Vitro
The incorporation of engineered nanoparticles (NPs) into everyday consumer goods, products, and applications has given rise to the field of nanotoxicology, which evaluates the safety of NPs within biological environments. The unique physicochemical properties of NPs have made this an insurmountable...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-07-01
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| Series: | Nanomaterials |
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| Online Access: | https://www.mdpi.com/2079-4991/11/7/1807 |
| _version_ | 1797526476616105984 |
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| author | Nicholas J. Braun Rachel M. Galaska Maggie E. Jewett Kristen A. Krupa |
| author_facet | Nicholas J. Braun Rachel M. Galaska Maggie E. Jewett Kristen A. Krupa |
| author_sort | Nicholas J. Braun |
| collection | DOAJ |
| description | The incorporation of engineered nanoparticles (NPs) into everyday consumer goods, products, and applications has given rise to the field of nanotoxicology, which evaluates the safety of NPs within biological environments. The unique physicochemical properties of NPs have made this an insurmountable challenge, as their reactivity and variable behavior have given rise to discrepancies between standard cell-based in vitro and animal in vivo models. In this study, enhanced in vitro models were generated that retained the advantages of traditional cell cultures, but incorporated the modifications of (1) inclusion of an activated immune element and (2) the presence of physiologically-relevant dynamic flow. Following verification that the human alveolar epithelial and macrophage (A549/U937) co-culture could be successfully sustained under both static and dynamic conditions, these cultures, in addition to a standard A549 static model, were challenged with 10 nm citrate coated silver NPs (AgNPs). This work identified a reshaping of the AgNP-cellular interface and differential biological responses following exposure. The presence of dynamic flow modified cellular morphology and reduced AgNP deposition by approximately 20% over the static exposure environments. Cellular toxicity and stress endpoints, including reactive oxygen species, heat shock protein 70, and secretion of pro-inflammatory cytokines, were found to vary as a function of both cellular composition and flow conditions; with activated macrophages and fluid flow both mitigating the severity of AgNP-dependent bioeffects. This work highlights the possibility of enhanced in vitro systems to assess the safety of engineered NPs and demonstrates their effectiveness in elucidating novel NP-cellular interactions and toxicological profiles. |
| first_indexed | 2024-03-10T09:29:47Z |
| format | Article |
| id | doaj.art-b82c4547522c429d8b50ea730fe177c0 |
| institution | Directory Open Access Journal |
| issn | 2079-4991 |
| language | English |
| last_indexed | 2024-03-10T09:29:47Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nanomaterials |
| spelling | doaj.art-b82c4547522c429d8b50ea730fe177c02023-11-22T04:34:12ZengMDPI AGNanomaterials2079-49912021-07-01117180710.3390/nano11071807Implementation of a Dynamic Co-Culture Model Abated Silver Nanoparticle Interactions and Nanotoxicological Outcomes In VitroNicholas J. Braun0Rachel M. Galaska1Maggie E. Jewett2Kristen A. Krupa3Molecular Bioeffects Branch, Human Effectiveness Directorate, Wright Patterson Air Force Base, Dayton, OH 45433, USADepartment of Chemical and Materials Engineering, University of Dayton, Dayton, OH 45469-0256, USADepartment of Chemical and Materials Engineering, University of Dayton, Dayton, OH 45469-0256, USADepartment of Chemical and Materials Engineering, University of Dayton, Dayton, OH 45469-0256, USAThe incorporation of engineered nanoparticles (NPs) into everyday consumer goods, products, and applications has given rise to the field of nanotoxicology, which evaluates the safety of NPs within biological environments. The unique physicochemical properties of NPs have made this an insurmountable challenge, as their reactivity and variable behavior have given rise to discrepancies between standard cell-based in vitro and animal in vivo models. In this study, enhanced in vitro models were generated that retained the advantages of traditional cell cultures, but incorporated the modifications of (1) inclusion of an activated immune element and (2) the presence of physiologically-relevant dynamic flow. Following verification that the human alveolar epithelial and macrophage (A549/U937) co-culture could be successfully sustained under both static and dynamic conditions, these cultures, in addition to a standard A549 static model, were challenged with 10 nm citrate coated silver NPs (AgNPs). This work identified a reshaping of the AgNP-cellular interface and differential biological responses following exposure. The presence of dynamic flow modified cellular morphology and reduced AgNP deposition by approximately 20% over the static exposure environments. Cellular toxicity and stress endpoints, including reactive oxygen species, heat shock protein 70, and secretion of pro-inflammatory cytokines, were found to vary as a function of both cellular composition and flow conditions; with activated macrophages and fluid flow both mitigating the severity of AgNP-dependent bioeffects. This work highlights the possibility of enhanced in vitro systems to assess the safety of engineered NPs and demonstrates their effectiveness in elucidating novel NP-cellular interactions and toxicological profiles.https://www.mdpi.com/2079-4991/11/7/1807silver nanoparticlenanotoxicologycellular co-culturedynamic flowreactive oxygen speciescytokine production |
| spellingShingle | Nicholas J. Braun Rachel M. Galaska Maggie E. Jewett Kristen A. Krupa Implementation of a Dynamic Co-Culture Model Abated Silver Nanoparticle Interactions and Nanotoxicological Outcomes In Vitro Nanomaterials silver nanoparticle nanotoxicology cellular co-culture dynamic flow reactive oxygen species cytokine production |
| title | Implementation of a Dynamic Co-Culture Model Abated Silver Nanoparticle Interactions and Nanotoxicological Outcomes In Vitro |
| title_full | Implementation of a Dynamic Co-Culture Model Abated Silver Nanoparticle Interactions and Nanotoxicological Outcomes In Vitro |
| title_fullStr | Implementation of a Dynamic Co-Culture Model Abated Silver Nanoparticle Interactions and Nanotoxicological Outcomes In Vitro |
| title_full_unstemmed | Implementation of a Dynamic Co-Culture Model Abated Silver Nanoparticle Interactions and Nanotoxicological Outcomes In Vitro |
| title_short | Implementation of a Dynamic Co-Culture Model Abated Silver Nanoparticle Interactions and Nanotoxicological Outcomes In Vitro |
| title_sort | implementation of a dynamic co culture model abated silver nanoparticle interactions and nanotoxicological outcomes in vitro |
| topic | silver nanoparticle nanotoxicology cellular co-culture dynamic flow reactive oxygen species cytokine production |
| url | https://www.mdpi.com/2079-4991/11/7/1807 |
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