Supramolecular Surface Functionalization of Iron Oxide Nanoparticles with α-Cyclodextrin-Based Cationic Star Polymer for Magnetically-Enhanced Gene Delivery

Supramolecular polymers formed through host–guest complexation have inspired many interesting developments of functional materials for biological and biomedical applications. Here, we report a novel design of a non-viral gene delivery system composed of a cationic star polymer forming supramolecular...

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Autores principales:	Hanyi Li, Erwin Peng, Feng Zhao, Jun Li, Junmin Xue
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	iron oxide magnetic nanoparticles supramolecular complexation cyclodextrin oligoethylenimine gene transfection Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/6e22152fb15246a19035217149a94139
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spelling	oai:doaj.org-article:6e22152fb15246a19035217149a941392021-11-25T18:41:27ZSupramolecular Surface Functionalization of Iron Oxide Nanoparticles with α-Cyclodextrin-Based Cationic Star Polymer for Magnetically-Enhanced Gene Delivery10.3390/pharmaceutics131118841999-4923https://doaj.org/article/6e22152fb15246a19035217149a941392021-11-01T00:00:00Zhttps://www.mdpi.com/1999-4923/13/11/1884https://doaj.org/toc/1999-4923Supramolecular polymers formed through host–guest complexation have inspired many interesting developments of functional materials for biological and biomedical applications. Here, we report a novel design of a non-viral gene delivery system composed of a cationic star polymer forming supramolecular complexes with the surface oleyl groups of superparamagnetic iron oxide nanoparticles (SPIONs), for magnetically enhanced delivery of DNA into mammalian cells. The cationic star polymer was synthesized by grafting multiple oligoethylenimine (OEI) chains onto an α-cyclodextrin (α-CD) core. The SPIONs were synthesized from iron(III) acetylacetonate and stabilized by hydrophobic oleic acid and oleylamine in hexane, which were characterized in terms of their size, structure, morphology, and magnetic properties. The synthesized magnetic particles were found to be superparamagnetic, making them a suitable ferrofluid for biological applications. In order to change the hydrophobic surface of the SPIONs to a hydrophilic surface with functionalities for plasmid DNA (pDNA) binding and gene delivery, a non-traditional but simple supramolecular surface modification process was used. The α-CD-OEI cationic star polymer was dissolved in water and then mixed with the SPIONs stabilized in hexane. The SPIONs were “pulled” into the water phase through the formation of supramolecular host–guest inclusion complexes between the α-CD unit and the oleyl surface of the SPIONs, while the surface of the SPIONs was changed to OEI cationic polymers. The α-CD-OEI-SPION complex could effectively bind and condense pDNA to form α-CD-OEI-SPION/pDNA polyplex nanoparticles at the size of ca. 200 nm suitable for delivery of genes into cells through endocytosis. The cytotoxicity of the α-CD-OEI-SPION complex was also found to be lower than high-molecular-weight polyethylenimine, which was widely studied previously as a standard non-viral gene vector. When gene transfection was carried out in the presence of an external magnetic field, the α-CD-OEI-SPION/pDNA polyplex nanoparticles greatly increased the gene transfection efficiency by nearly tenfold. Therefore, the study has demonstrated a facile two-in-one method to make the SPIONs water-soluble as well as functionalized for enhanced magnetofection.Hanyi LiErwin PengFeng ZhaoJun LiJunmin XueMDPI AGarticleiron oxidemagnetic nanoparticlessupramolecular complexationcyclodextrinoligoethyleniminegene transfectionPharmacy and materia medicaRS1-441ENPharmaceutics, Vol 13, Iss 1884, p 1884 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	iron oxide magnetic nanoparticles supramolecular complexation cyclodextrin oligoethylenimine gene transfection Pharmacy and materia medica RS1-441
spellingShingle	iron oxide magnetic nanoparticles supramolecular complexation cyclodextrin oligoethylenimine gene transfection Pharmacy and materia medica RS1-441 Hanyi Li Erwin Peng Feng Zhao Jun Li Junmin Xue Supramolecular Surface Functionalization of Iron Oxide Nanoparticles with α-Cyclodextrin-Based Cationic Star Polymer for Magnetically-Enhanced Gene Delivery
description	Supramolecular polymers formed through host–guest complexation have inspired many interesting developments of functional materials for biological and biomedical applications. Here, we report a novel design of a non-viral gene delivery system composed of a cationic star polymer forming supramolecular complexes with the surface oleyl groups of superparamagnetic iron oxide nanoparticles (SPIONs), for magnetically enhanced delivery of DNA into mammalian cells. The cationic star polymer was synthesized by grafting multiple oligoethylenimine (OEI) chains onto an α-cyclodextrin (α-CD) core. The SPIONs were synthesized from iron(III) acetylacetonate and stabilized by hydrophobic oleic acid and oleylamine in hexane, which were characterized in terms of their size, structure, morphology, and magnetic properties. The synthesized magnetic particles were found to be superparamagnetic, making them a suitable ferrofluid for biological applications. In order to change the hydrophobic surface of the SPIONs to a hydrophilic surface with functionalities for plasmid DNA (pDNA) binding and gene delivery, a non-traditional but simple supramolecular surface modification process was used. The α-CD-OEI cationic star polymer was dissolved in water and then mixed with the SPIONs stabilized in hexane. The SPIONs were “pulled” into the water phase through the formation of supramolecular host–guest inclusion complexes between the α-CD unit and the oleyl surface of the SPIONs, while the surface of the SPIONs was changed to OEI cationic polymers. The α-CD-OEI-SPION complex could effectively bind and condense pDNA to form α-CD-OEI-SPION/pDNA polyplex nanoparticles at the size of ca. 200 nm suitable for delivery of genes into cells through endocytosis. The cytotoxicity of the α-CD-OEI-SPION complex was also found to be lower than high-molecular-weight polyethylenimine, which was widely studied previously as a standard non-viral gene vector. When gene transfection was carried out in the presence of an external magnetic field, the α-CD-OEI-SPION/pDNA polyplex nanoparticles greatly increased the gene transfection efficiency by nearly tenfold. Therefore, the study has demonstrated a facile two-in-one method to make the SPIONs water-soluble as well as functionalized for enhanced magnetofection.
format	article
author	Hanyi Li Erwin Peng Feng Zhao Jun Li Junmin Xue
author_facet	Hanyi Li Erwin Peng Feng Zhao Jun Li Junmin Xue
author_sort	Hanyi Li
title	Supramolecular Surface Functionalization of Iron Oxide Nanoparticles with α-Cyclodextrin-Based Cationic Star Polymer for Magnetically-Enhanced Gene Delivery
title_short	Supramolecular Surface Functionalization of Iron Oxide Nanoparticles with α-Cyclodextrin-Based Cationic Star Polymer for Magnetically-Enhanced Gene Delivery
title_full	Supramolecular Surface Functionalization of Iron Oxide Nanoparticles with α-Cyclodextrin-Based Cationic Star Polymer for Magnetically-Enhanced Gene Delivery
title_fullStr	Supramolecular Surface Functionalization of Iron Oxide Nanoparticles with α-Cyclodextrin-Based Cationic Star Polymer for Magnetically-Enhanced Gene Delivery
title_full_unstemmed	Supramolecular Surface Functionalization of Iron Oxide Nanoparticles with α-Cyclodextrin-Based Cationic Star Polymer for Magnetically-Enhanced Gene Delivery
title_sort	supramolecular surface functionalization of iron oxide nanoparticles with α-cyclodextrin-based cationic star polymer for magnetically-enhanced gene delivery
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/6e22152fb15246a19035217149a94139
work_keys_str_mv	AT hanyili supramolecularsurfacefunctionalizationofironoxidenanoparticleswithacyclodextrinbasedcationicstarpolymerformagneticallyenhancedgenedelivery AT erwinpeng supramolecularsurfacefunctionalizationofironoxidenanoparticleswithacyclodextrinbasedcationicstarpolymerformagneticallyenhancedgenedelivery AT fengzhao supramolecularsurfacefunctionalizationofironoxidenanoparticleswithacyclodextrinbasedcationicstarpolymerformagneticallyenhancedgenedelivery AT junli supramolecularsurfacefunctionalizationofironoxidenanoparticleswithacyclodextrinbasedcationicstarpolymerformagneticallyenhancedgenedelivery AT junminxue supramolecularsurfacefunctionalizationofironoxidenanoparticleswithacyclodextrinbasedcationicstarpolymerformagneticallyenhancedgenedelivery
_version_	1718410777893797888

Supramolecular Surface Functionalization of Iron Oxide Nanoparticles with α-Cyclodextrin-Based Cationic Star Polymer for Magnetically-Enhanced Gene Delivery

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