Biocompatible coated magnetosome minerals with various organization and cellular interaction properties induce cytotoxicity towards RG-2 and GL-261 glioma cells in the presence of an alternating magnetic field

Abstract

BackgroundBiologics magnetics nanoparticles, magnetosomes, attract attention because of their magnetic characteristics and potential applications. The aim of the present study was to develop and characterize novel magnetosomes, which were extracted from magnetotactic bacteria, purified to produce apyrogen magnetosome minerals, and then coated with Chitosan, Neridronate, or Polyethyleneimine. It yielded stable magnetosomes designated as M-Chi, M-Neri, and M-PEI, respectively. Nanoparticle biocompatibility was evaluated on mouse fibroblast cells (3T3), mouse glioblastoma cells (GL-261) and rat glioblastoma cells (RG-2). We also tested these nanoparticles for magnetic hyperthermia treatment of tumor in vitro on two tumor cell lines GL-261 and RG-2 under the application of an alternating magnetic field. Heating, efficacy and internalization properties were then evaluated.ResultsNanoparticles coated with chitosan, polyethyleneimine and neridronate are apyrogen, biocompatible and stable in aqueous suspension. The presence of a thin coating in M-Chi and M-PEI favors an arrangement in chains of the magnetosomes, similar to that observed in magnetosomes directly extracted from magnetotactic bacteria, while the thick matrix embedding M-Neri leads to structures with an average thickness of 3.5 µm2 per magnetosome mineral. In the presence of GL-261 cells and upon the application of an alternating magnetic field, M-PEI and M-Chi lead to the highest specific absorption rates of 120–125 W/gFe. Furthermore, while M-Chi lead to rather low rates of cellular internalization, M-PEI strongly associate to cells, a property modulated by the application of an alternating magnetic field.ConclusionsCoating of purified magnetosome minerals can therefore be chosen to control the interactions of nanoparticles with cells, organization of the minerals, as well as heating and cytotoxicity properties, which are important parameters to be considered in the design of a magnetic hyperthermia treatment of tumor.Electronic supplementary materialThe online version of this article (doi:10.1186/s12951-017-0293-2) contains supplementary material, which is available to authorized users.

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...…”

“…Separately, a number of studies have used bacterial magnetosomes as an alternative for chemically synthesized MNPs. In comparison to conventional MIONPs, those studies report that bacterial magnetosomes can maintain tumor temperatures at 43-46 C for longer, have higher antitumor efficacy in GBM cell lines, and require lower AMF amplitude to achieve target temperatures [174][175][176][177]. One potential issue MHT is facing is that high concentrations of MNPs are often required to reach the clinically needed thermal dose.…”

Natural Metallic Nanoparticles for Application in Nano-Oncology

“…a laser or an alternating magnetic field, heat appears to be the dominant mechanism of action since tumor disappearance is not observed in the absence of heat, and magnetosomes are therefore classifiable as medical devices. [54,85], (ii) a mechanism of tumor cell death dominated by apoptosis as was observed during in vitro studies where magnetosomes were brought into contact with GBM cells and then exposed to one magnetic session [53,84], (iii) anti-tumor activity due to the presence of the magnetosomes within tumor margin, (iv) the attraction of certain immune cells, such as PNN, in the region where magnetosomes are located, even so a direct link between the anti-tumor activity and the presence of PNN has not yet been established [53,84]. Table 2 summarizes the in vitro and in vivo anti-tumor efficacies obtained with the various types of nanoparticles presented in table 1.…”

“…Figure 4 illustrates, through a series of fours schematic diagrams, the different mechanisms that could be involved in the anti-tumor activity, i.e.,: (i) localized heat induced at magnetosome location that could occur inside or outside tumor cells, depending on whether (or not) magnetosomes have internalized in tumor cells [ 54 , 85 ], (ii) a mechanism of tumor cell death dominated by apoptosis as was observed during in vitro studies where magnetosomes were brought into contact with GBM cells and then exposed to one magnetic session [ 53 , 84 ], (iii) anti-tumor activity due to the presence of the magnetosomes within tumor margin, (iv) the attraction of certain immune cells, such as PNN, in the region where magnetosomes are located, even so a direct link between the anti-tumor activity and the presence of PNN has not yet been established [ 53 , 84 ]. In cases where magnetosomes are heated under the application of radiation, e.g.…”

Improved methods for mass production of magnetosomes and applications: a review

“…Deduced endotoxin concentration can be further verified by in vivo experiments. Hamdous et al [38], in their study, examined the endotoxin concentrations by administering the purified magnetosome suspension in the rabbits' ear. The induction of any fever among rabbits was indicated the pyrogenic or non-pyrogenic suspensions.…”