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Hyaluronan Nanoparticles Selectively Target Plaque-Associated Macrophages and Improve Plaque Stability in Atherosclerosis
[Image: see text] Hyaluronan is a biologically active polymer, which can be formulated into nanoparticles. In our study, we aimed to probe atherosclerosis-associated inflammation by using hyaluronan nanoparticles and to determine whether they can ameliorate atherosclerosis. Hyaluronan nanoparticles...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American
Chemical Society
2017
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5492212/ https://www.ncbi.nlm.nih.gov/pubmed/28463501 http://dx.doi.org/10.1021/acsnano.7b01385 |
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author | Beldman, Thijs J. Senders, Max L. Alaarg, Amr Pérez-Medina, Carlos Tang, Jun Zhao, Yiming Fay, Francois Deichmöller, Jacqueline Born, Benjamin Desclos, Emilie van der Wel, Nicole N. Hoebe, Ron A. Kohen, Fortune Kartvelishvily, Elena Neeman, Michal Reiner, Thomas Calcagno, Claudia Fayad, Zahi A. de Winther, Menno P. J. Lutgens, Esther Mulder, Willem J. M. Kluza, Ewelina |
author_facet | Beldman, Thijs J. Senders, Max L. Alaarg, Amr Pérez-Medina, Carlos Tang, Jun Zhao, Yiming Fay, Francois Deichmöller, Jacqueline Born, Benjamin Desclos, Emilie van der Wel, Nicole N. Hoebe, Ron A. Kohen, Fortune Kartvelishvily, Elena Neeman, Michal Reiner, Thomas Calcagno, Claudia Fayad, Zahi A. de Winther, Menno P. J. Lutgens, Esther Mulder, Willem J. M. Kluza, Ewelina |
author_sort | Beldman, Thijs J. |
collection | PubMed |
description | [Image: see text] Hyaluronan is a biologically active polymer, which can be formulated into nanoparticles. In our study, we aimed to probe atherosclerosis-associated inflammation by using hyaluronan nanoparticles and to determine whether they can ameliorate atherosclerosis. Hyaluronan nanoparticles (HA-NPs) were prepared by reacting amine-functionalized oligomeric hyaluronan (HA) with cholanic ester and labeled with a fluorescent or radioactive label. HA-NPs were characterized in vitro by several advanced microscopy methods. The targeting properties and biodistribution of HA-NPs were studied in apoe(–/–) mice, which received either fluorescent or radiolabeled HA-NPs and were examined ex vivo by flow cytometry or nuclear techniques. Furthermore, three atherosclerotic rabbits received (89)Zr-HA-NPs and were imaged by PET/MRI. The therapeutic effects of HA-NPs were studied in apoe(–/–) mice, which received weekly doses of 50 mg/kg HA-NPs during a 12-week high-fat diet feeding period. Hydrated HA-NPs were ca. 90 nm in diameter and displayed very stable morphology under hydrolysis conditions. Flow cytometry revealed a 6- to 40-fold higher uptake of Cy7-HA-NPs by aortic macrophages compared to normal tissue macrophages. Interestingly, both local and systemic HA-NP–immune cell interactions significantly decreased over the disease progression. (89)Zr-HA-NPs-induced radioactivity in atherosclerotic aortas was 30% higher than in wild-type controls. PET imaging of rabbits revealed 6-fold higher standardized uptake values compared to the muscle. The plaques of HA-NP-treated mice contained 30% fewer macrophages compared to control and free HA-treated group. In conclusion, we show favorable targeting properties of HA-NPs, which can be exploited for PET imaging of atherosclerosis-associated inflammation. Furthermore, we demonstrate the anti-inflammatory effects of HA-NPs in atherosclerosis. |
format | Online Article Text |
id | pubmed-5492212 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | American
Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-54922122017-07-03 Hyaluronan Nanoparticles Selectively Target Plaque-Associated Macrophages and Improve Plaque Stability in Atherosclerosis Beldman, Thijs J. Senders, Max L. Alaarg, Amr Pérez-Medina, Carlos Tang, Jun Zhao, Yiming Fay, Francois Deichmöller, Jacqueline Born, Benjamin Desclos, Emilie van der Wel, Nicole N. Hoebe, Ron A. Kohen, Fortune Kartvelishvily, Elena Neeman, Michal Reiner, Thomas Calcagno, Claudia Fayad, Zahi A. de Winther, Menno P. J. Lutgens, Esther Mulder, Willem J. M. Kluza, Ewelina ACS Nano [Image: see text] Hyaluronan is a biologically active polymer, which can be formulated into nanoparticles. In our study, we aimed to probe atherosclerosis-associated inflammation by using hyaluronan nanoparticles and to determine whether they can ameliorate atherosclerosis. Hyaluronan nanoparticles (HA-NPs) were prepared by reacting amine-functionalized oligomeric hyaluronan (HA) with cholanic ester and labeled with a fluorescent or radioactive label. HA-NPs were characterized in vitro by several advanced microscopy methods. The targeting properties and biodistribution of HA-NPs were studied in apoe(–/–) mice, which received either fluorescent or radiolabeled HA-NPs and were examined ex vivo by flow cytometry or nuclear techniques. Furthermore, three atherosclerotic rabbits received (89)Zr-HA-NPs and were imaged by PET/MRI. The therapeutic effects of HA-NPs were studied in apoe(–/–) mice, which received weekly doses of 50 mg/kg HA-NPs during a 12-week high-fat diet feeding period. Hydrated HA-NPs were ca. 90 nm in diameter and displayed very stable morphology under hydrolysis conditions. Flow cytometry revealed a 6- to 40-fold higher uptake of Cy7-HA-NPs by aortic macrophages compared to normal tissue macrophages. Interestingly, both local and systemic HA-NP–immune cell interactions significantly decreased over the disease progression. (89)Zr-HA-NPs-induced radioactivity in atherosclerotic aortas was 30% higher than in wild-type controls. PET imaging of rabbits revealed 6-fold higher standardized uptake values compared to the muscle. The plaques of HA-NP-treated mice contained 30% fewer macrophages compared to control and free HA-treated group. In conclusion, we show favorable targeting properties of HA-NPs, which can be exploited for PET imaging of atherosclerosis-associated inflammation. Furthermore, we demonstrate the anti-inflammatory effects of HA-NPs in atherosclerosis. American Chemical Society 2017-05-02 2017-06-27 /pmc/articles/PMC5492212/ /pubmed/28463501 http://dx.doi.org/10.1021/acsnano.7b01385 Text en Copyright © 2017 American Chemical Society This is an open access article published under a Creative Commons Non-Commercial No Derivative Works (CC-BY-NC-ND) Attribution License (http://pubs.acs.org/page/policy/authorchoice_ccbyncnd_termsofuse.html) , which permits copying and redistribution of the article, and creation of adaptations, all for non-commercial purposes. |
spellingShingle | Beldman, Thijs J. Senders, Max L. Alaarg, Amr Pérez-Medina, Carlos Tang, Jun Zhao, Yiming Fay, Francois Deichmöller, Jacqueline Born, Benjamin Desclos, Emilie van der Wel, Nicole N. Hoebe, Ron A. Kohen, Fortune Kartvelishvily, Elena Neeman, Michal Reiner, Thomas Calcagno, Claudia Fayad, Zahi A. de Winther, Menno P. J. Lutgens, Esther Mulder, Willem J. M. Kluza, Ewelina Hyaluronan Nanoparticles Selectively Target Plaque-Associated Macrophages and Improve Plaque Stability in Atherosclerosis |
title | Hyaluronan
Nanoparticles Selectively Target Plaque-Associated Macrophages and
Improve Plaque Stability in Atherosclerosis |
title_full | Hyaluronan
Nanoparticles Selectively Target Plaque-Associated Macrophages and
Improve Plaque Stability in Atherosclerosis |
title_fullStr | Hyaluronan
Nanoparticles Selectively Target Plaque-Associated Macrophages and
Improve Plaque Stability in Atherosclerosis |
title_full_unstemmed | Hyaluronan
Nanoparticles Selectively Target Plaque-Associated Macrophages and
Improve Plaque Stability in Atherosclerosis |
title_short | Hyaluronan
Nanoparticles Selectively Target Plaque-Associated Macrophages and
Improve Plaque Stability in Atherosclerosis |
title_sort | hyaluronan
nanoparticles selectively target plaque-associated macrophages and
improve plaque stability in atherosclerosis |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5492212/ https://www.ncbi.nlm.nih.gov/pubmed/28463501 http://dx.doi.org/10.1021/acsnano.7b01385 |
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