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Factors Affecting Intracellular Delivery and Release of Hydrophilic Versus Hydrophobic Cargo from Mesoporous Silica Nanoparticles on 2D and 3D Cell Cultures

Intracellular drug delivery by mesoporous silica nanoparticles (MSNs) carrying hydrophilic and hydrophobic fluorophores as model drug cargo is demonstrated on 2D cellular and 3D tumor organoid level. Two different MSN designs, chosen on the basis of the characteristics of the loaded cargo, were used...

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Autores principales: Desai, Diti, Åkerfelt, Malin, Prabhakar, Neeraj, Toriseva, Mervi, Näreoja, Tuomas, Zhang, Jixi, Nees, Matthias, Rosenholm, Jessica M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6320991/
https://www.ncbi.nlm.nih.gov/pubmed/30453596
http://dx.doi.org/10.3390/pharmaceutics10040237
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author Desai, Diti
Åkerfelt, Malin
Prabhakar, Neeraj
Toriseva, Mervi
Näreoja, Tuomas
Zhang, Jixi
Nees, Matthias
Rosenholm, Jessica M.
author_facet Desai, Diti
Åkerfelt, Malin
Prabhakar, Neeraj
Toriseva, Mervi
Näreoja, Tuomas
Zhang, Jixi
Nees, Matthias
Rosenholm, Jessica M.
author_sort Desai, Diti
collection PubMed
description Intracellular drug delivery by mesoporous silica nanoparticles (MSNs) carrying hydrophilic and hydrophobic fluorophores as model drug cargo is demonstrated on 2D cellular and 3D tumor organoid level. Two different MSN designs, chosen on the basis of the characteristics of the loaded cargo, were used: MSNs with a surface-grown poly(ethylene imine), PEI, coating only for hydrophobic cargo and MSNs with lipid bilayers covalently coupled to the PEI layer as a diffusion barrier for hydrophilic cargo. First, the effect of hydrophobicity corresponding to loading degree (hydrophobic cargo) as well as surface charge (hydrophilic cargo) on intracellular drug release was studied on the cellular level. All incorporated agents were able to release to varying degrees from the endosomes into the cytoplasm in a loading degree (hydrophobic) or surface charge (hydrophilic) dependent manner as detected by live cell imaging. When administered to organotypic 3D tumor models, the hydrophilic versus hydrophobic cargo-carrying MSNs showed remarkable differences in labeling efficiency, which in this case also corresponds to drug delivery efficacy in 3D. The obtained results could thus indicate design aspects to be taken into account for the development of efficacious intracellular drug delivery systems, especially in the translation from standard 2D culture to more biologically relevant organotypic 3D cultures.
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spelling pubmed-63209912019-01-11 Factors Affecting Intracellular Delivery and Release of Hydrophilic Versus Hydrophobic Cargo from Mesoporous Silica Nanoparticles on 2D and 3D Cell Cultures Desai, Diti Åkerfelt, Malin Prabhakar, Neeraj Toriseva, Mervi Näreoja, Tuomas Zhang, Jixi Nees, Matthias Rosenholm, Jessica M. Pharmaceutics Article Intracellular drug delivery by mesoporous silica nanoparticles (MSNs) carrying hydrophilic and hydrophobic fluorophores as model drug cargo is demonstrated on 2D cellular and 3D tumor organoid level. Two different MSN designs, chosen on the basis of the characteristics of the loaded cargo, were used: MSNs with a surface-grown poly(ethylene imine), PEI, coating only for hydrophobic cargo and MSNs with lipid bilayers covalently coupled to the PEI layer as a diffusion barrier for hydrophilic cargo. First, the effect of hydrophobicity corresponding to loading degree (hydrophobic cargo) as well as surface charge (hydrophilic cargo) on intracellular drug release was studied on the cellular level. All incorporated agents were able to release to varying degrees from the endosomes into the cytoplasm in a loading degree (hydrophobic) or surface charge (hydrophilic) dependent manner as detected by live cell imaging. When administered to organotypic 3D tumor models, the hydrophilic versus hydrophobic cargo-carrying MSNs showed remarkable differences in labeling efficiency, which in this case also corresponds to drug delivery efficacy in 3D. The obtained results could thus indicate design aspects to be taken into account for the development of efficacious intracellular drug delivery systems, especially in the translation from standard 2D culture to more biologically relevant organotypic 3D cultures. MDPI 2018-11-17 /pmc/articles/PMC6320991/ /pubmed/30453596 http://dx.doi.org/10.3390/pharmaceutics10040237 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Desai, Diti
Åkerfelt, Malin
Prabhakar, Neeraj
Toriseva, Mervi
Näreoja, Tuomas
Zhang, Jixi
Nees, Matthias
Rosenholm, Jessica M.
Factors Affecting Intracellular Delivery and Release of Hydrophilic Versus Hydrophobic Cargo from Mesoporous Silica Nanoparticles on 2D and 3D Cell Cultures
title Factors Affecting Intracellular Delivery and Release of Hydrophilic Versus Hydrophobic Cargo from Mesoporous Silica Nanoparticles on 2D and 3D Cell Cultures
title_full Factors Affecting Intracellular Delivery and Release of Hydrophilic Versus Hydrophobic Cargo from Mesoporous Silica Nanoparticles on 2D and 3D Cell Cultures
title_fullStr Factors Affecting Intracellular Delivery and Release of Hydrophilic Versus Hydrophobic Cargo from Mesoporous Silica Nanoparticles on 2D and 3D Cell Cultures
title_full_unstemmed Factors Affecting Intracellular Delivery and Release of Hydrophilic Versus Hydrophobic Cargo from Mesoporous Silica Nanoparticles on 2D and 3D Cell Cultures
title_short Factors Affecting Intracellular Delivery and Release of Hydrophilic Versus Hydrophobic Cargo from Mesoporous Silica Nanoparticles on 2D and 3D Cell Cultures
title_sort factors affecting intracellular delivery and release of hydrophilic versus hydrophobic cargo from mesoporous silica nanoparticles on 2d and 3d cell cultures
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6320991/
https://www.ncbi.nlm.nih.gov/pubmed/30453596
http://dx.doi.org/10.3390/pharmaceutics10040237
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