Magnetic Polyion Complex Micelles for Cell Toxicity Induced by Radiofrequency Magnetic Field Hyperthermia

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.

<p>Thermosensitive Betulinic Acid-Loaded Magnetoliposomes: A Promising Antitumor Potential for Highly Aggressive Human Breast Adenocarcinoma Cells Under Hyperthermic Conditions</p>

“…Inducing hyperthermia in breast carcinomas presents a series of advantages as the normal cells surrounding the tumor tissue exhibit a higher resistance to temperatures around 43–46 °C, while tumor cells are known to be significantly affected by hyperthermia treatment, up to 46 °C 8 – 12 . Nevertheless, hyperthermia treatment success is based on biocompatible temperatures, up to 46 °C, 8 – 11 exceeding this temperature will induce necrosis of both normal and tumor cells. 13 In recent years, magnetic nanoparticles (MNPs) have been developed and gained significant attention in drug delivery, hyperthermia approach, and remote-controlled drug release 10 , 12 , 14 – 17 .…”

In vitro exploration of the synergistic effect of alternating magnetic field mediated thermo–chemotherapy with doxorubicin loaded dual pH- and thermo-responsive magnetic nanocomposite carriers

“…One of the unsolved issues is to determine which magnetic hyperthermia implementation method is superior: 23 intracellular hyperthermia which means that the nanoparticles either have been internalized into the cells or tightly deposited onto the cells, and then heated the cells directly; or extracellular hyperthermia, indicating that the thermal damages are produced through the extracellular matrix (ECM) temperature elevation or ECM mechanical disruption. 24 The proponents for intercellular hyperthermia demonstrated that it could provide a destructive effect despite the absence of macroscopic temperature increase, [25][26][27][28][29] like obtained by with intra-tumour injection and the extracellular approach. However, the effects varied among reported work in the literature.…”

Hyperthermia treatment advances for brain tumors

“…Tapeinos et al [194] Preclinical Human GBM (U87-MG) Lipid-based magnetic nanovectors (LMNVs) Babincova et al [195] Preclinical Human GBM (U87-MG) Etoposide-carrying human serum albumin immobilized magnetic nanoparticles Babincova et al [191] Preclinical Rodent glioma (C6) Thermosensitive magnetoliposomes containing SPIONs and doxorubicin Jia et al 2018 [189] Preclinical Human GBM (U251) RGE-modified, SPION-, and Cur-loaded exosomes (RGE-Exo-SPION/Cur) Lu et al [188] Preclinical Human GBM (U251) Cetuximab (C225)-encapsulated core-shell Fe 3 O 4 @Au magnetic nanoparticles Nguyen et al [173] Preclinical Human GBM (U87-MG) Fluorescently labeled MPIC micelles (G1@Fe 3 O 4 ) Shirvalilou et al [168] Preclinical Rodent glioma (C6) 5-Iodo-2-deoxyuridine (IUdR)-loaded magnetic nanoparticles (NGO/PLGA) Zhou et al, 2018 [187] Preclinical Human GBM (U87-MG) c(RGDyK) peptide PEGylated Fe@Fe 3 O 4 nanoparticles (RGD-PEG-MNPs) Alphand ery et al [175,176] Preclinical Human GBM (U87-MG-Luc) Magnetosomes (CM) Hamdous et al [177] Preclinical Rodent glioma (GL261 þ RG2); Chitosan (M-Chi), polyethyleneimine (M-PEI), and neridronate (M-Neri) coated nanoparticles Le Fevre et al [174] Preclinical Rodent glioma (GL261) Magnetosomes-poly-L-lysine (M-PLL) and iron oxide nanoparticles Ohtake et al [196] Preclinical Human GBM (U87-MG þ U251 þ YKG) Fe(Salen) nanoparticles Zamora-Mora et al [192] Preclinical Human GBM (A-172) Chitosan nanoparticles (CSNPs) Liu et al [169] Preclinical Human GBM (U87-MG) Ferromagnetic IMO nanoflowers (FIMO-NFs) Shevstov et al [185] Preclinical Rodent glioma (C6) Superparamagnetic iron oxide nanoparticles conjugated with heat shock protein (Hsp70-SPIONs) Pala et al [186] Preclinical Human GBM (U87-MG) Dextran-coated, aptamer-bound, aptamer-fluorescein magnetic NPs (NPAF) Yi et al [162] Preclinical Rodent glioma (C6) Magnetic nano-iron Jiang et al [178] Preclinical Human GBM (U251) Silver nanoparticles (AgNPs) Meenach et al [250] Preclinical Human GBM (M059K) Magnetic PEG-based hydrogel nanocomposites Zhao et al [197] Preclinical Human GBM (U251) Solar-planet structured magnetic nanocomposites (Amino silane coated magnetic nanoparticles) Hua et al [198] Preclinical Rodent glioma (C6) Polymer poly[aniline-co-N-(1-one-butyric acid) aniline] (SPAnH) coated iron oxide nanoparticles Liu et al [179] Preclinical Human GBM (U251); Rodent glioma (C6) Silver nanoparticles (Ag...…”

“…Instead of coating the NPs, one group encapsulated magnetite (Fe 3 O 4 ) NPs within copolymer-based micelles as a way of increasing the colloidal stability and controlling the size and shape of the contained MIONPs. When used to perform MHT, these magnetic polyion complex micelles reduced cell viability in glioma cells at a concentration of iron 3 orders of magnitude lower than concentrations used in previous clinical trials [173]. Separately, a number of studies have used bacterial magnetosomes as an alternative for chemically synthesized MNPs.…”