In vitro nanoparticle dosimetry for adherent growing cell monolayers covering bottom and lateral walls

Abstract Background Even though a continuously high number of in vitro studies on nanoparticles are being published, the issue of correct dose matter is often not sufficiently taken into account. Due to their size, the diffusion of nanoparticles is slower, as compared to soluble chemicals, and they...

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Main Authors: Linda Böhmert, Laura König, Holger Sieg, Dajana Lichtenstein, Niklas Paul, Albert Braeuning, Andreas Voigt, Alfonso Lampen
Format: Article
Language:English
Published: BMC 2018-10-01
Series:Particle and Fibre Toxicology
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12989-018-0278-9
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author Linda Böhmert
Laura König
Holger Sieg
Dajana Lichtenstein
Niklas Paul
Albert Braeuning
Andreas Voigt
Alfonso Lampen
author_facet Linda Böhmert
Laura König
Holger Sieg
Dajana Lichtenstein
Niklas Paul
Albert Braeuning
Andreas Voigt
Alfonso Lampen
author_sort Linda Böhmert
collection DOAJ
description Abstract Background Even though a continuously high number of in vitro studies on nanoparticles are being published, the issue of correct dose matter is often not sufficiently taken into account. Due to their size, the diffusion of nanoparticles is slower, as compared to soluble chemicals, and they sediment slowly. Therefore, the administered dose of particles in in vitro experiments is not necessarily the same (effective) dose that comes into contact with the cellular system. This can lead to misinterpretations of experimental toxic effects and disturbs the meaningfulness of in vitro studies. In silico calculations of the effective nanoparticle dose can help circumventing this problem. Results This study addresses more complex in vitro models like the human intestinal cell line Caco-2 or the human liver cell line HepaRG, which need to be differentiated over a few weeks to reach their full complexity. During the differentiation time the cells grow up the wall of the cell culture dishes and therefore a three-dimensional-based in silico model of the nanoparticle dose was developed to calculate the administered dose received by different cell populations at the bottom and the walls of the culture dish. Moreover, the model can perform calculations based on the hydrodynamic diameter which is measured by light scattering methods, or based on the diffusion coefficient measured by nanoparticle tracking analysis (NTA). This 3DSDD (3D-sedimentation-diffusion-dosimetry) model was experimentally verified against existing dosimetry models and was applied to differentiated Caco-2 cells incubated with silver nanoparticles. Conclusions The 3DSDD accounts for the 3D distribution of cells in in vitro cell culture dishes and is therefore suitable for differentiated cells. To encourage the use of dosimetry calculating software, our model can be downloaded from the supporting information.
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spelling doaj.art-199c307025e943aa80a657cc48da451e2022-12-22T01:16:49ZengBMCParticle and Fibre Toxicology1743-89772018-10-0115112010.1186/s12989-018-0278-9In vitro nanoparticle dosimetry for adherent growing cell monolayers covering bottom and lateral wallsLinda Böhmert0Laura König1Holger Sieg2Dajana Lichtenstein3Niklas Paul4Albert Braeuning5Andreas Voigt6Alfonso Lampen7Department of Food Safety, German Federal Institute for Risk AssessmentChair of Process Systems Engineering, Otto-von-Guericke University MagdeburgDepartment of Food Safety, German Federal Institute for Risk AssessmentDepartment of Food Safety, German Federal Institute for Risk AssessmentTechnische Universität BerlinDepartment of Food Safety, German Federal Institute for Risk AssessmentChair of Process Systems Engineering, Otto-von-Guericke University MagdeburgDepartment of Food Safety, German Federal Institute for Risk AssessmentAbstract Background Even though a continuously high number of in vitro studies on nanoparticles are being published, the issue of correct dose matter is often not sufficiently taken into account. Due to their size, the diffusion of nanoparticles is slower, as compared to soluble chemicals, and they sediment slowly. Therefore, the administered dose of particles in in vitro experiments is not necessarily the same (effective) dose that comes into contact with the cellular system. This can lead to misinterpretations of experimental toxic effects and disturbs the meaningfulness of in vitro studies. In silico calculations of the effective nanoparticle dose can help circumventing this problem. Results This study addresses more complex in vitro models like the human intestinal cell line Caco-2 or the human liver cell line HepaRG, which need to be differentiated over a few weeks to reach their full complexity. During the differentiation time the cells grow up the wall of the cell culture dishes and therefore a three-dimensional-based in silico model of the nanoparticle dose was developed to calculate the administered dose received by different cell populations at the bottom and the walls of the culture dish. Moreover, the model can perform calculations based on the hydrodynamic diameter which is measured by light scattering methods, or based on the diffusion coefficient measured by nanoparticle tracking analysis (NTA). This 3DSDD (3D-sedimentation-diffusion-dosimetry) model was experimentally verified against existing dosimetry models and was applied to differentiated Caco-2 cells incubated with silver nanoparticles. Conclusions The 3DSDD accounts for the 3D distribution of cells in in vitro cell culture dishes and is therefore suitable for differentiated cells. To encourage the use of dosimetry calculating software, our model can be downloaded from the supporting information.http://link.springer.com/article/10.1186/s12989-018-0278-9Dosimetry modelsSilver nanoparticlesDifferentiated Caco-2 cellsIn vitro
spellingShingle Linda Böhmert
Laura König
Holger Sieg
Dajana Lichtenstein
Niklas Paul
Albert Braeuning
Andreas Voigt
Alfonso Lampen
In vitro nanoparticle dosimetry for adherent growing cell monolayers covering bottom and lateral walls
Particle and Fibre Toxicology
Dosimetry models
Silver nanoparticles
Differentiated Caco-2 cells
In vitro
title In vitro nanoparticle dosimetry for adherent growing cell monolayers covering bottom and lateral walls
title_full In vitro nanoparticle dosimetry for adherent growing cell monolayers covering bottom and lateral walls
title_fullStr In vitro nanoparticle dosimetry for adherent growing cell monolayers covering bottom and lateral walls
title_full_unstemmed In vitro nanoparticle dosimetry for adherent growing cell monolayers covering bottom and lateral walls
title_short In vitro nanoparticle dosimetry for adherent growing cell monolayers covering bottom and lateral walls
title_sort in vitro nanoparticle dosimetry for adherent growing cell monolayers covering bottom and lateral walls
topic Dosimetry models
Silver nanoparticles
Differentiated Caco-2 cells
In vitro
url http://link.springer.com/article/10.1186/s12989-018-0278-9
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