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Cyclodextrin-Appended Superparamagnetic Iron Oxide Nanoparticles as Cholesterol-Mopping Agents
Cholesterol plays a crucial role in major cardiovascular and neurodegenerative diseases, including Alzheimer’s disease and rare genetic disorders showing altered cholesterol metabolism. Cyclodextrins (CDs) have shown promising therapeutic efficacy based on their capacity to sequester and mobilise ch...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8636776/ https://www.ncbi.nlm.nih.gov/pubmed/34869239 http://dx.doi.org/10.3389/fchem.2021.795598 |
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author | Puglisi, Antonino Bassini, Simone Reimhult, Erik |
author_facet | Puglisi, Antonino Bassini, Simone Reimhult, Erik |
author_sort | Puglisi, Antonino |
collection | PubMed |
description | Cholesterol plays a crucial role in major cardiovascular and neurodegenerative diseases, including Alzheimer’s disease and rare genetic disorders showing altered cholesterol metabolism. Cyclodextrins (CDs) have shown promising therapeutic efficacy based on their capacity to sequester and mobilise cholesterol. However, the administration of monomeric CDs suffers from several drawbacks due to their lack of specificity and poor pharmacokinetics. We present core-shell superparamagnetic iron oxide nanoparticles (SPIONs) functionalised with CDs appended to poly (2-methyl-2-oxazoline) polymers grafted in a dense brush to the iron oxide core. The CD-decorated nanoparticles (CySPIONs) are designed so that the macrocycle is specifically cleaved off the nanoparticle’s shell at a slightly acidic pH. In the intended use, free monomeric CDs will then mobilise cholesterol out of the lysosome to the cytosol and beyond through the formation of an inclusion complex. Hence, its suitability as a therapeutic platform to remove cholesterol in the lysosomal compartment. Synthesis and full characterization of the polymer as well as of the core-shell SPION are presented. Cholesterol-binding activity is shown through an enzymatic assay. |
format | Online Article Text |
id | pubmed-8636776 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-86367762021-12-03 Cyclodextrin-Appended Superparamagnetic Iron Oxide Nanoparticles as Cholesterol-Mopping Agents Puglisi, Antonino Bassini, Simone Reimhult, Erik Front Chem Chemistry Cholesterol plays a crucial role in major cardiovascular and neurodegenerative diseases, including Alzheimer’s disease and rare genetic disorders showing altered cholesterol metabolism. Cyclodextrins (CDs) have shown promising therapeutic efficacy based on their capacity to sequester and mobilise cholesterol. However, the administration of monomeric CDs suffers from several drawbacks due to their lack of specificity and poor pharmacokinetics. We present core-shell superparamagnetic iron oxide nanoparticles (SPIONs) functionalised with CDs appended to poly (2-methyl-2-oxazoline) polymers grafted in a dense brush to the iron oxide core. The CD-decorated nanoparticles (CySPIONs) are designed so that the macrocycle is specifically cleaved off the nanoparticle’s shell at a slightly acidic pH. In the intended use, free monomeric CDs will then mobilise cholesterol out of the lysosome to the cytosol and beyond through the formation of an inclusion complex. Hence, its suitability as a therapeutic platform to remove cholesterol in the lysosomal compartment. Synthesis and full characterization of the polymer as well as of the core-shell SPION are presented. Cholesterol-binding activity is shown through an enzymatic assay. Frontiers Media S.A. 2021-11-18 /pmc/articles/PMC8636776/ /pubmed/34869239 http://dx.doi.org/10.3389/fchem.2021.795598 Text en Copyright © 2021 Puglisi, Bassini and Reimhult. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Chemistry Puglisi, Antonino Bassini, Simone Reimhult, Erik Cyclodextrin-Appended Superparamagnetic Iron Oxide Nanoparticles as Cholesterol-Mopping Agents |
title | Cyclodextrin-Appended Superparamagnetic Iron Oxide Nanoparticles as Cholesterol-Mopping Agents |
title_full | Cyclodextrin-Appended Superparamagnetic Iron Oxide Nanoparticles as Cholesterol-Mopping Agents |
title_fullStr | Cyclodextrin-Appended Superparamagnetic Iron Oxide Nanoparticles as Cholesterol-Mopping Agents |
title_full_unstemmed | Cyclodextrin-Appended Superparamagnetic Iron Oxide Nanoparticles as Cholesterol-Mopping Agents |
title_short | Cyclodextrin-Appended Superparamagnetic Iron Oxide Nanoparticles as Cholesterol-Mopping Agents |
title_sort | cyclodextrin-appended superparamagnetic iron oxide nanoparticles as cholesterol-mopping agents |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8636776/ https://www.ncbi.nlm.nih.gov/pubmed/34869239 http://dx.doi.org/10.3389/fchem.2021.795598 |
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