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...

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Main Authors: Antonino Puglisi, Simone Bassini, Erik Reimhult
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-11-01
Series:Frontiers in Chemistry
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fchem.2021.795598/full
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author Antonino Puglisi
Simone Bassini
Simone Bassini
Erik Reimhult
author_facet Antonino Puglisi
Simone Bassini
Simone Bassini
Erik Reimhult
author_sort Antonino Puglisi
collection DOAJ
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.
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spelling doaj.art-e5e84b09d59b4e81b8910a2b65724af32022-12-21T20:47:39ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462021-11-01910.3389/fchem.2021.795598795598Cyclodextrin-Appended Superparamagnetic Iron Oxide Nanoparticles as Cholesterol-Mopping AgentsAntonino Puglisi0Simone Bassini1Simone Bassini2Erik Reimhult3Department of Nanobiotechnology, Institute of Biologically Inspired Materials, University of Natural Resources and Life Sciences (BOKU), Vienna, AustriaDepartment of Nanobiotechnology, Institute of Biologically Inspired Materials, University of Natural Resources and Life Sciences (BOKU), Vienna, AustriaLife Sciences Department, University of Modena and Reggio Emilia, Modena, ItalyDepartment of Nanobiotechnology, Institute of Biologically Inspired Materials, University of Natural Resources and Life Sciences (BOKU), Vienna, AustriaCholesterol 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.https://www.frontiersin.org/articles/10.3389/fchem.2021.795598/fullcholesterolcyclodextrinSPIONcore-shell nanoparticlesnanoparticles
spellingShingle Antonino Puglisi
Simone Bassini
Simone Bassini
Erik Reimhult
Cyclodextrin-Appended Superparamagnetic Iron Oxide Nanoparticles as Cholesterol-Mopping Agents
Frontiers in Chemistry
cholesterol
cyclodextrin
SPION
core-shell nanoparticles
nanoparticles
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 cholesterol
cyclodextrin
SPION
core-shell nanoparticles
nanoparticles
url https://www.frontiersin.org/articles/10.3389/fchem.2021.795598/full
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