Abstract
Magnetic nanoparticles (MNPs) of magnetite (Fe3O4) were prepared using a polystyrene-graft-poly(2-vinylpyridine) copolymer (denoted G0PS-g-P2VP or G1) as template. These MNPs were subjected to self-assembly with a poly(acrylic acid)-block-poly(2-hydroxyethyl acrylate) double-hydrophilic block copolymer (DHBC), PAA-b-PHEA, to form water-dispersible magnetic polyion complex (MPIC) micelles. Large Fe3O4 crystallites were visualized by transmission electron microscopy (TEM) and magnetic suspensions of MPIC micelles exhibited improved colloidal stability in aqueous environments over a wide pH and ionic strength range. Biological cells incubated for 48 h with MPIC micelles at the highest concentration (1250 µg of Fe3O4 per mL) had a cell viability of 91%, as compared with 51% when incubated with bare (unprotected) MNPs. Cell internalization, visualized by confocal laser scanning microscopy (CLSM) and TEM, exhibited strong dependence on the MPIC micelle concentration and incubation time, as also evidenced by fluorescence-activated cell sorting (FACS). The usefulness of MPIC micelles for cellular radiofrequency magnetic field hyperthermia (MFH) was also confirmed, as the MPIC micelles showed a dual dose-dependent effect (concentration and duration of magnetic field exposure) on the viability of L929 mouse fibroblasts and U87 human glioblastoma epithelial cells.
Highlights
Superparamagnetic iron oxide nanoparticles (SPIONs) have received significant attention for uses in targeted drug delivery [1,2,3], as magnetic resonance imaging contrast agents [4,5] and as heat mediators in the magnetic hyperthermia treatment of tumours [6,7,8]
An in vitro study of magnetic field hyperthermia (MFH) was performed on two different cell lines selected for different reasons: mouse L929 fibroblasts, a non-cancerous immortalized cell line recommended in the ISO10993-1: 2009 procedure “Biological evaluation of medical devices” [28] and in view of the foreseen medical application, U87 human glioblastoma epithelial cells, the high grade brain tumour cells targeted in the first clinical trials with magnetic hyperthermia used in combination with conventional radiotherapy [29]
Unimolecular micelles made from a G1 arborescent copolymer (G0PS-g-P2VP) were used as templates to control the size and improve the size distribution of iron oxide Magnetic nanoparticles (MNPs)
Summary
Superparamagnetic iron oxide nanoparticles (SPIONs) have received significant attention for uses in targeted drug delivery [1,2,3], as magnetic resonance imaging contrast agents [4,5] and as heat mediators in the magnetic hyperthermia treatment of tumours [6,7,8]. An in vitro study of magnetic field hyperthermia (MFH) was performed on two different cell lines selected for different reasons: mouse L929 fibroblasts, a non-cancerous immortalized cell line recommended in the ISO10993-1: 2009 procedure “Biological evaluation of medical devices” [28] and in view of the foreseen medical application, U87 human glioblastoma epithelial cells, the high grade brain tumour cells targeted in the first clinical trials with magnetic hyperthermia used in combination with conventional radiotherapy [29] In both cases, a colloidal suspension of MNPs (the MPIC micelles) was incubated with the cells, allowing the MNPs to be internalized through the cell membrane. Cell AMF-induced cell toxicity yet without increase of temperature, ascribed to thermal losses in the cell aqueous medium of high thermal conductivity, is discussed at the end of the article within the context of recent published works on intracellular magnetic hyperthermia
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