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Pharmaceutics
Volume 10
Issue 4
10.3390/pharmaceutics10040237
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Article

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

by
Diti Desai
1,
Malin Åkerfelt
2,
Neeraj Prabhakar
1,3,
Mervi Toriseva
2,
Tuomas Näreoja
4,
Jixi Zhang
5,
Matthias Nees
2 and
Jessica M. Rosenholm
1,*
1
Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, 20521 Turku, Finland
2
Institute of Biomedicine, University of Turku, 20520 Turku, Finland
3
Cell Biology, Faculty of Science and Engineering, Åbo Akademi University, 20521 Turku, Finland
4
Department of Laboratory Medicine, Division of Pathology, Karolinska Institute, 14186 Stockholm, Sweden
5
College of Bioengineering, Chongqing University, Chongqing 400044, China
*
Author to whom correspondence should be addressed.
Pharmaceutics 2018, 10(4), 237; https://doi.org/10.3390/pharmaceutics10040237
Received: 31 October 2018 / Revised: 13 November 2018 / Accepted: 15 November 2018 / Published: 17 November 2018
(This article belongs to the Special Issue Porous Inorganic Drug Delivery Systems)
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Abstract

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. View Full-Text
Keywords: intracellular delivery; mesoporous silica nanoparticles; cargo hydrophilicity; cargo hydrophobicity; cancer cells; cell labeling; organotypic 3D culture; live-cell imaging intracellular delivery; mesoporous silica nanoparticles; cargo hydrophilicity; cargo hydrophobicity; cancer cells; cell labeling; organotypic 3D culture; live-cell imaging
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
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MDPI and ACS Style

Desai, D.; Åkerfelt, M.; Prabhakar, N.; Toriseva, M.; Näreoja, T.; Zhang, J.; Nees, M.; Rosenholm, J.M. Factors Affecting Intracellular Delivery and Release of Hydrophilic Versus Hydrophobic Cargo from Mesoporous Silica Nanoparticles on 2D and 3D Cell Cultures. Pharmaceutics 2018, 10, 237. https://doi.org/10.3390/pharmaceutics10040237

AMA Style

Desai D, Åkerfelt M, Prabhakar N, Toriseva M, Näreoja T, Zhang J, Nees M, Rosenholm JM. Factors Affecting Intracellular Delivery and Release of Hydrophilic Versus Hydrophobic Cargo from Mesoporous Silica Nanoparticles on 2D and 3D Cell Cultures. Pharmaceutics. 2018; 10(4):237. https://doi.org/10.3390/pharmaceutics10040237

Chicago/Turabian Style

Desai, Diti, Malin Åkerfelt, Neeraj Prabhakar, Mervi Toriseva, Tuomas Näreoja, Jixi Zhang, Matthias Nees, and Jessica M. Rosenholm. 2018. "Factors Affecting Intracellular Delivery and Release of Hydrophilic Versus Hydrophobic Cargo from Mesoporous Silica Nanoparticles on 2D and 3D Cell Cultures" Pharmaceutics 10, no. 4: 237. https://doi.org/10.3390/pharmaceutics10040237

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