Magnetic nanoparticles as bimodal tools in magnetically induced labelling and magnetic heating of tumour cells: an<i>in vitro</i>study

Kettering, Melanie; Winter, J G; Zeisberger, Matthias; Bremer-Streck, Sibylle; Oehring, H; Bergemann, Christian; Hergt, R.; Kj, Halbhuber; Kaiser, Werner A.; Hilger, Ingrid

doi:10.1088/0957-4484/18/17/175101

Cited by 60 publications

(59 citation statements)

References 40 publications

(59 reference statements)

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“…It is worth mentioning that Kettering et al previously employed ARA-MNPs for magnetic labeling and the heating of tumor cells. 20 The larger saturation magnetization M S (78 and 49 Am 2 / kg, for PLL-MNPs and ARA-MNPs, respectively) revealed that our homemade nanoparticles were consistent with the higher efficiency observed in the cell migration experiments, since the magnetic force exerted on a single cell is proportional to the magnetic moment of the incorporated MNPs for a given magnetic field value (and its spatial derivative).…”

Section: Resultssupporting

confidence: 81%

“…The commercial ARA-MNPs particles selected for this purpose were previously studied for labeling and heating purposes. 20 ARA-MNPs showed a larger hydrodynamic radius due to the presence of a polymeric matrix on the magnetic core and lower magnetic properties in terms of magnetization saturation and coercivity.…”

Section: Comparison Between Pll-coated and Commercial Fe 3 O 4 Mnpsmentioning

confidence: 99%

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Poly-l-lysine-coated magnetic nanoparticles as intracellular actuators for neural guidance

Riggio

Calatayud

Hoskins

et al. 2012

IJN

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Purpose: It has been proposed in the literature that Fe 3 O 4 magnetic nanoparticles (MNPs) could be exploited to enhance or accelerate nerve regeneration and to provide guidance for regenerating axons. MNPs could create mechanical tension that stimulates the growth and elongation of axons. Particles suitable for this purpose should possess (1) high saturation magnetization, (2) a negligible cytotoxic profile, and (3) a high capacity to magnetize mammalian cells. Unfortunately, the materials currently available on the market do not satisfy these criteria; therefore, this work attempts to overcome these deficiencies. Methods: Magnetite particles were synthesized by an oxidative hydrolysis method and characterized based on their external morphology and size distribution (high-resolution transmission electron microscopy [HR-TEM]) as well as their colloidal (Z potential) and magnetic properties (Superconducting QUantum Interference Devices [SQUID]). Cell viability was assessed via Trypan blue dye exclusion assay, cell doubling time, and MTT cell proliferation assay and reactive oxygen species production. Particle uptake was monitored via Prussian blue staining, intracellular iron content quantification via a ferrozine-based assay, and direct visualization by dual-beam (focused ion beam/scanning electron microscopy [FIB/SEM]) analysis. Experiments were performed on human neuroblastoma SH-SY5Y cell line and primary Schwann cell cultures of the peripheral nervous system. Results: This paper reports on the synthesis and characterization of polymer-coated magnetic Fe 3 O 4 nanoparticles with an average diameter of 73 ± 6 nm that are designed as magnetic actuators for neural guidance. The cells were able to incorporate quantities of iron up to 2 pg/cell. The intracellular distribution of MNPs obtained by optical and electronic microscopy showed large structures of MNPs crossing the cell membrane into the cytoplasm, thus rendering them suitable for magnetic manipulation by external magnetic fields. Specifically, migration experiments under external magnetic fields confirmed that these MNPs can effectively actuate the cells, thus inducing measurable migration towards predefined directions more effectively than commercial nanoparticles (fluidMAG-ARA supplied by Chemicell). There were no observable toxic effects from MNPs on cell viability for working concentrations of 10 µg/mL (EC 25 of 20.8 µg/mL, compared to 12 µg/ mL in fluidMAG-ARA). Cell proliferation assays performed with primary cell cultures of the peripheral nervous system confirmed moderate cytotoxicity (EC 25 of 10.35 µg/mL). Conclusion: These results indicate that loading neural cells with the proposed MNPs is likely to be an effective strategy for promoting non-invasive neural regeneration through cell magnetic actuation.

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Section: Resultssupporting

confidence: 81%

Section: Comparison Between Pll-coated and Commercial Fe 3 O 4 Mnpsmentioning

confidence: 99%

Poly-l-lysine-coated magnetic nanoparticles as intracellular actuators for neural guidance

Riggio

Calatayud

Hoskins

et al. 2012

IJN

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“…19 Although several publications reported that especially smaller MNP (approximately between 20 nm and 100 nm) were preferentially taken up by tumor cells (eg, by endocytosis), the possibility of the used MNP to be taken up by BT474 tumor cells or, at least, be bound to their membrane was verified in previous experiments. [20][21][22] Two hours after the application of thermoablative temperatures in the tumor region, a downregulation of BCL2 and FGF-R1 was found whereas HSP70 remained unchanged. Additionally, more apoptotic and necrotic areas were visible in close proximity to regions with high nanoparticle concentration in the treatment group (group 1) compared to the control group (group 2), indicating the eradication of tumor cells by using heat as a physical stressor.…”

Section: Discussionmentioning

confidence: 99%

Magnetic thermoablation stimuli alter BCL2 and FGF-R1 but not HSP70 expression profiles in BT474 breast tumors

Stapf¹,

Pömpner²,

Kettering³

et al. 2015

IJN

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Magnetically induced heating of magnetic nanoparticles (MNP) in an alternating magnetic field (AMF) is a promising minimal invasive tool for localized tumor treatment that eradicates tumor cells by applying thermal stress. While temperatures between 42°C and 45°C induce apoptosis and sensitize the cells for chemo- and radiation therapies when applied for at least 30 minutes, temperatures above 50°C, so-called thermoablative temperatures, rapidly induce irreversible cell damage resulting in necrosis. Since only little is known concerning the protein expression of anti-apoptotic B-cell lymphoma 2 (BCL2), fibroblast growth factor receptor 1 (FGF-R1), and heat shock protein (HSP70) after short-time magnetic thermoablative tumor treatment, these relevant tumor proteins were investigated by immunohistochemistry (IHC) in a human BT474 breast cancer mouse xenograft model. In the investigated sample groups, the application of thermoablative temperatures (<2 minutes) led to a downregulation of BCL2 and FGF-R1 on the protein level while the level of HSP70 remained unchanged. Coincidently, the tumor tissue was damaged by heat, resulting in large apoptotic and necrotic areas in regions with high MNP concentration. Taken together, thermoablative heating induced via magnetic methods can reduce the expression of tumor-related proteins and locally inactivate tumor tissue, leading to a prospectively reduced tumorigenicity of cancerous tissues. The presented data allow a deeper insight into the molecular mechanisms in relation to magnetic thermoablative tumor treatments with the aim of further improvements.

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“…We could show that magnetically based cellular MNP uptake by human adenocarcinoma cells is because of suitable magnetic field gradients that intensify the temperature increase generated during magnetic heating [20]. These strategies will provide new means to avoid the occurrence of regions of temperature underdosage during magnetic hyperthermia.…”

Section: The Intratumoral Temperature Pattern Might Well Be Influencementioning

confidence: 99%

Means to increase the therapeutic efficiency of magnetic heating of tumors

Kettering

Grau

Pömpner

et al. 2015

Biomedical Engineering / Biomedizinische Technik

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Abstract:The treatment of tumors via hyperthermia has gained increased attention in the last years. Among the different modalities available so far, magnetic hyperthermia has the particular advantage of offering the possibility of depositing the heating source directly into the tumor. In this study, we summarized the present knowledge we gained on how to improve the therapeutic efficiency of magnetic hyperthermia using magnetic nanoparticles (MNPs), with particular consideration of the intratumoral infiltration of the magnetic material. We found that (1) MNPs will be mainly immobilized at the tumor area and that this aspect has to be considered when estimating the heating potential of MNPs, (2) the intratumoral distribution patterns via slow infiltration might well be modulated by specific MNP coating and magnetic targeting, (3) imaging of the nanoparticle depositions within the tumor might allow to correct the distribution pattern via multiple applications, (4) multiple therapeutic sessions are feasible because MNPs are not delivered from the tumor site during the heating process, (5) the utilization of MNPs that internalize into cells will favor the production of intracellular heating spots rather than extracellular ones, (6) utilization of MNPs functionalized with chemotherapeutic agents will allow us to exploit the additive effects of both therapeutic modalities, and (7) distinct cytopathological and histopathological alterations in target tissues are induced as a result of magnetic hyperthermia. However, the accumulation at the tumor via intravenous application remains a matter of challenge.

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Magnetic nanoparticles as bimodal tools in magnetically induced labelling and magnetic heating of tumour cells: anin vitrostudy

Cited by 60 publications

References 40 publications

Poly-l-lysine-coated magnetic nanoparticles as intracellular actuators for neural guidance

Poly-l-lysine-coated magnetic nanoparticles as intracellular actuators for neural guidance

Magnetic thermoablation stimuli alter BCL2 and FGF-R1 but not HSP70 expression profiles in BT474 breast tumors

Means to increase the therapeutic efficiency of magnetic heating of tumors

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