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Amphiphilic nanogels: influence of surface hydrophobicity on protein corona, biocompatibility and cellular uptake
BACKGROUND AND PURPOSE: Nanogels (NGs) are promising drug delivery tools but are typically limited to hydrophilic drugs. Many potential new drugs are hydrophobic. Our study systematically investigates amphiphilic NGs with varying hydrophobicity, but similar colloidal features to ensure comparability...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6769055/ https://www.ncbi.nlm.nih.gov/pubmed/31576128 http://dx.doi.org/10.2147/IJN.S215935 |
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author | Bewersdorff, Tony Gruber, Alexandra Eravci, Murat Dumbani, Malti Klinger, Daniel Haase, Andrea |
author_facet | Bewersdorff, Tony Gruber, Alexandra Eravci, Murat Dumbani, Malti Klinger, Daniel Haase, Andrea |
author_sort | Bewersdorff, Tony |
collection | PubMed |
description | BACKGROUND AND PURPOSE: Nanogels (NGs) are promising drug delivery tools but are typically limited to hydrophilic drugs. Many potential new drugs are hydrophobic. Our study systematically investigates amphiphilic NGs with varying hydrophobicity, but similar colloidal features to ensure comparability. The amphiphilic NGs used in this experiment consist of a hydrophilic polymer network with randomly distributed hydrophobic groups. For the synthesis we used a new synthetic platform approach. Their amphiphilic character allows the encapsulation of hydrophobic drugs. Importantly, the hydrophilic/hydrophobic balance determines drug loading and biological interactions. In particular, protein adsorption to NG surfaces is dependent on hydrophobicity and critically determines circulation time. Our study investigates how network hydrophobicity influences protein binding, biocompatibility and cellular uptake. METHODS: Biocompatibility of the NGs was examined by WST-1 assay in monocytic-like THP-1 cells. Serum protein corona formation was investigated using dynamic light scattering and two-dimensional gel electrophoresis. Proteins were identified by liquid chromatography-tandem mass spectrometry. In addition, cellular uptake was analyzed via flow cytometry. RESULTS: All NGs were highly biocompatible. The protein binding patterns for the two most hydrophobic NGs were very similar to each other but clearly different from the hydrophilic ones. Overall, protein binding was increased with increasing hydrophobicity, resulting in increased cellular uptake. CONCLUSION: Our study supports the establishment of structure–property relationships and contributes to the accurate balance between maximum loading capacity with low protein binding, optimal biological half-life and good biocompatibility. This is an important step to derive design principles of amphiphilic NGs to be applied as drug delivery vehicles. |
format | Online Article Text |
id | pubmed-6769055 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-67690552019-10-01 Amphiphilic nanogels: influence of surface hydrophobicity on protein corona, biocompatibility and cellular uptake Bewersdorff, Tony Gruber, Alexandra Eravci, Murat Dumbani, Malti Klinger, Daniel Haase, Andrea Int J Nanomedicine Original Research BACKGROUND AND PURPOSE: Nanogels (NGs) are promising drug delivery tools but are typically limited to hydrophilic drugs. Many potential new drugs are hydrophobic. Our study systematically investigates amphiphilic NGs with varying hydrophobicity, but similar colloidal features to ensure comparability. The amphiphilic NGs used in this experiment consist of a hydrophilic polymer network with randomly distributed hydrophobic groups. For the synthesis we used a new synthetic platform approach. Their amphiphilic character allows the encapsulation of hydrophobic drugs. Importantly, the hydrophilic/hydrophobic balance determines drug loading and biological interactions. In particular, protein adsorption to NG surfaces is dependent on hydrophobicity and critically determines circulation time. Our study investigates how network hydrophobicity influences protein binding, biocompatibility and cellular uptake. METHODS: Biocompatibility of the NGs was examined by WST-1 assay in monocytic-like THP-1 cells. Serum protein corona formation was investigated using dynamic light scattering and two-dimensional gel electrophoresis. Proteins were identified by liquid chromatography-tandem mass spectrometry. In addition, cellular uptake was analyzed via flow cytometry. RESULTS: All NGs were highly biocompatible. The protein binding patterns for the two most hydrophobic NGs were very similar to each other but clearly different from the hydrophilic ones. Overall, protein binding was increased with increasing hydrophobicity, resulting in increased cellular uptake. CONCLUSION: Our study supports the establishment of structure–property relationships and contributes to the accurate balance between maximum loading capacity with low protein binding, optimal biological half-life and good biocompatibility. This is an important step to derive design principles of amphiphilic NGs to be applied as drug delivery vehicles. Dove 2019-09-26 /pmc/articles/PMC6769055/ /pubmed/31576128 http://dx.doi.org/10.2147/IJN.S215935 Text en © 2019 Bewersdorff et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Bewersdorff, Tony Gruber, Alexandra Eravci, Murat Dumbani, Malti Klinger, Daniel Haase, Andrea Amphiphilic nanogels: influence of surface hydrophobicity on protein corona, biocompatibility and cellular uptake |
title | Amphiphilic nanogels: influence of surface hydrophobicity on protein corona, biocompatibility and cellular uptake |
title_full | Amphiphilic nanogels: influence of surface hydrophobicity on protein corona, biocompatibility and cellular uptake |
title_fullStr | Amphiphilic nanogels: influence of surface hydrophobicity on protein corona, biocompatibility and cellular uptake |
title_full_unstemmed | Amphiphilic nanogels: influence of surface hydrophobicity on protein corona, biocompatibility and cellular uptake |
title_short | Amphiphilic nanogels: influence of surface hydrophobicity on protein corona, biocompatibility and cellular uptake |
title_sort | amphiphilic nanogels: influence of surface hydrophobicity on protein corona, biocompatibility and cellular uptake |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6769055/ https://www.ncbi.nlm.nih.gov/pubmed/31576128 http://dx.doi.org/10.2147/IJN.S215935 |
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