Magnetic particle hyperthermia--a promising tumour therapy?

We present a critical review of the state of the art of magnetic particle hyperthermia (MPH) as a minimal invasive tumour therapy. Magnetic principles of heating mechanisms are discussed with respect to the optimum choice of nanoparticle properties. In particular, the relation between superparamagnetic and ferrimagnetic single domain nanoparticles is clarified in order to choose the appropriate particle size distribution and the role of particle mobility for the relaxation path is discussed. Knowledge of the effect of particle properties for achieving high specific heating power provides necessary guidelines for development of nanoparticles tailored for tumour therapy. Nanoscale heat transfer processes are discussed with respect to the achievable temperature increase in cancer cells. The need to realize a well-controlled temperature distribution in tumour tissue represents the most serious problem of MPH, at present. Visionary concepts of particle administration, in particular by means of antibody targeting, are far from clinical practice, yet. On the basis of current knowledge of treating cancer by thermal damaging, this article elucidates possibilities, prospects, and challenges for establishment of MPH as a standard medical procedure.

Magnetic nanoparticle heating and heat transfer on a microscale: Basic principles, realities and physical limitations of hyperthermia for tumour therapy.

In this review article we present basic principles of magnetically induced heat generation of magnetic nanoparticles for application in magnetic particle hyperthermia. After explanation of heating mechanisms, the role of particle-particle as well as particle-tissue interactions is discussed with respect to achievable heating power of the particles inside the tumour. On the basis of heat transfer theory at the micro-scale, the balance between generated and dissipated heat inside the tumour and the resulting damaging effects for biological tissue is examined. The heating behaviour as a function of tumour size is examined in combination with feasible field strength and frequency. Numerical calculations and experimental investigations are used to show the lower tumour size limit for tumour heating to therapeutically suitable temperatures. In summary, this article illuminates practical aspects, limitations, and the state of the art for the application of magnetic heating in magnetic particle hyperthermia as thermal treatment of small tumours.

Validity limits of the Néel relaxation model of magnetic nanoparticles for hyperthermia.

The derivation of the optimum mean diameter of magnetic nanoparticles (MNP) for hyperthermia as a tumour therapy in the literature is commonly reduced to application of the Néel relaxation model. Serious restrictions of this model for MNP for hyperthermia are discussed and a way is outlined to a more comprehensive model including hysteresis.

Characterization of iron oxide nanoparticles adsorbed with cisplatin for biomedical applications.

The aim of this study was to characterize the behaviour of cisplatin adsorbed magnetic nanoparticles (cis-MNPs) for minimal invasive cancer treatments in preliminary in vitro investigations. Cisplatin was adsorbed to magnetic nanoparticles (MNPs) by simple incubation. For stability determinations, cis-MNPs were incubated in dH(2)O, phosphate-buffered saline (PBS) and fetal calf serum (FCS) at 4-121 degrees C up to 20 weeks. Hydrodynamic diameters were measured using laser diffraction. The extent of cisplatin linkage was determined by atomic absorption spectrometry. The magnetite core size was assessed by vibrating sample magnetometry and transmission electron microscopy. The specific loss power (SLP) was measured in an alternating magnetic field. Our results showed that a maximum of 10.3 +/- 1.6 (dH(2)O), 10 +/- 1.6 (PBS) and 13.4 +/- 2.2 (FCS) mg cisplatin g(-1) Fe could be adsorbed to MNPs. With hyperthermal (42 degrees C) or thermal ablative (60 degrees C) temperatures, used for therapeutic approaches, cisplatin did not desorb from cis-MNPs in dH(2)O during incubation times of 180 or 30 min, respectively. In PBS and FCS, cisplatin amounts adsorbed to MNPs decreased rapidly to approximately 50% and 25% at these temperatures. This cisplatin release will be necessary for successful chemotherapeutic activity and should increase the therapeutic effect of magnetic heating treatment in medicinal applications. The hydrodynamic diameters of MNPs or cis-MNPs were around 70 nm and magnetization data showed superparamagnetic behaviour. The obtained mean core diameter was around 12 nm. The SLP of the sample was calculated to be 75.5 +/- 1.6 W g(-1). In conclusion, cis-MNPs exhibit advantageous features for a facilitated desorption of cisplatin in biological media and the heating potential is adequate for hyperthermic treatments. Therefore, even though further detailed investigations are still necessary, tentative use in local tumour therapies aiming at a specific chemotherapeutic release in combination with magnetic heating seems to be feasible in the long term.

Effects of size distribution on hysteresis losses of magnetic nanoparticles for hyperthermia.

For understanding hysteresis losses of magnetic nanoparticles to be used for magnetic particle hyperthermia the effect of size distribution on the dependence of hysteresis losses on magnetic field amplitude is studied on the basis of a phenomenological model in the size range from superparamagnetism to magnetic multi-domains-roughly 10 up to 100 nm. Relying on experimental data for the size dependence of coercivity, an empirical expression for the dependence of hysteresis loss on field amplitude and particle size is derived for hypothetical monodisperse particle ensembles. Considering experimentally observable size distributions, the dependence of loss on distribution parameters-mean particle size and variance-is studied. There, field amplitude is taken into account as an important parameter, which for technical and biomedical reasons in hyperthermia equipment is restricted. Experimental results for different particle types with mean diameter of 30 nm may be well reproduced theoretically if a small loss contribution of Rayleigh type is taken into account. Results show that the Stoner-Wohlfarth model for single domain magnetization reversal via homogeneous rotation cannot explain experimental observations. In particular, in magnetosomes which are distinguished by nearly ideal crystallographic shapes and narrow size distribution large friction-like losses occur even for small field amplitude. Parameters of the high frequency field for hyperthermia (amplitude and frequency) as well as of the size distribution of applied particles are discussed with respect to attaining maximum specific heating power.

Thermal ablation of tumors using magnetic nanoparticles: an in vivo feasibility study.

RATIONALE AND OBJECTIVE: Feasibility of a new interventional procedure for the treatment of breast cancer called "magnetic thermal ablation" was examined under in vivo animal conditions. The method consists in the intratumoral application of iron oxide particles and the exposure of the breast to an alternating magnetic field, whereby the tumor is eliminated by heat. MATERIALS AND METHODS: Human breast adenocarcinomas were implanted into 45 immunodeficient SCID mice. Defined magnetite particle masses (between 4 mg and 18 mg per 100 mg tumor tissue) were injected intratumorally. Approximately 20 minutes later, animals were exposed to an alternating current (AC) magnetic field (amplitude: 6.5 kA/m, frequency: 400 kHz) for 4 minutes while measuring the temperature at defined tumor positions and at the rectum. The method efficacy was determined by the following end points: the assessment of the deposited heat dosages (DHD) at the defined locations within the target. The DHD was defined as the area between the time-dependent temperature curves during treatments and the temperature level without heating; histologic examinations of tumor tissue after heating; and the evaluation of the particle wash-out from the tumor by determining the percentage of injected iron doses per g tissue of selected organs (atomic absorption spectrometry; 50 minutes postinjection). RESULTS: Temperature increases between 12 degrees C and 73 degrees C were registered at different tumor locations (tumor center and periphery). The corresponding DHD ranged between 40 degrees C and 262 degrees C x minutes. Regions of DHD underdosage (lower than approximately 47-61 degrees C x min) were observed in 8 of 36 tumors. 2.4% to 22.3% of the injected iron dose per g dried tissues other than the tumor was detected after 50 minutes postinjection. Histologic examinations showed the presence of early stages of coagulation necrosis in treated tumor cells. DISCUSSION AND CONCLUSION: The data indicate that the proposed method allows the generation of localized heat spots at the tumor area. According to the histologic analysis and previous investigations the DHD were, in principle, high enough to kill tumor cells. The reasons for the presence of regions of temperature underdosage are discussed in the text. Special attention should be paid on the particle wash out in organs in the vicinity of the breast.

Heating potential of iron oxides for therapeutic purposes in interventional radiology.

RATIONALE AND OBJECTIVES: In addition to their diagnostic applications, iron oxides could be used therapeutically to eliminate tumors with heat if their heating powers are adequate. The authors therefore examined the specific absorption rate (SAR) of different iron oxide (magnetite) samples suspended in water and in liquid or solidified gel. MATERIALS AND METHODS: The authors compared two ferromagnetic fine powders (total particle size, >350 nm and 100 nm), five superparamagnetic ferrofluidic samples (total particle size, 10-280 nm), and a commercially available contrast medium (ferumoxides injectable solution, Endorem). The SARs of the magnetic material-suspended in distilled water or in liquid or solid agar-were estimated from time-dependent calorimetric measurements during exposure to an alternating current magnetic field (amplitude, 6.5 kA/m; frequency, 400 kHz). RESULTS: SARs varied considerably between the different iron oxide samples. The highest value was found for a ferrofluidic sample (>93 W/g), while Endorem had little heating power (<0.1 W/g). The SAR was clearly dependent on the aggregation state of the matrix only for the large-particle-size ferromagnetic sample, yielding the highest values for particle suspensions in water (74 W/g) and lowest for solid agar (8 W/g). The heating power of the smaller-particle-size ferromagnetic sample did not exceed 8 W/g. CONCLUSION: Heating powers differed according to the interaction of multiple physical parameters. Iron oxides should be selected carefully for therapeutic applications in magnetic heating.