Magnetic nanoparticles for biomedical applications

Magnetic nanoparticles (MNPs) having a size in the submicrometer range are promising novel tools in biomedical engineering. One of the most exciting recent developments was the invention of magnetic particle imaging (MPI), a medical imaging technique that enables the direct observation of magnetic tracers in living tissue with a high temporal and spatial resolution, combined with a high sensitivity. Two years ago a special issue of Biomedical Engineering appeared with a focus on this technique [3]. The papers of that issue treated various aspects of MPI, i.e. in particular, diagnostic potential [2] and safety aspects [5] in medical applications [23], measurement technique [7, 25] and data acquisition concepts [11, 14, 24], and synthesis [15], design [1, 8], and characterisation [17, 18, 27] of magnetic nanoparticles that promise the best performance as MPI-tracers.

The current topical issue highlights in a more general way the application of magnetic nanoparticles in biomedicine. It comprises a series of original research reports and reviews, reflecting the collaboration of scientists and engineers from various disciplines: physics, electrical engineering, material science, pharmacy, biology and biochemistry, and, of course, medical science with many subdisciplines, such as, e.g. oncology, cardiovascular medicine, radiology, to mention just a few. Some of the papers were financially supported by Deutsche Forschungsgemeinschaft in the frame of PAK151 [6, 13, 16, 19, 20].

Already a long time before MPI was invented, a number of in-vivo applications of iron oxide nanoparticles had been introduced in biomedical research that make use of their special magnetic properties. MNPs may serve as probes in living tissue that can be controlled non-invasively from the outside by an applied external magnetic field, while the magnetic action on the diamagnetic tissue around is negligible. In the absence of an external field, the magnetic moments of an ensemble of magnetic nanoparticles in thermal equilibrium will be randomly oriented and no net magnetic moment will be seen at a distance from the assembly. In a static homogeneous magnetic field H, however, the magnetic moments of the nanoparticles tend to align along the field direction, giving rise to a net magnetic moment that is measurable from the outside. From such measurements information can be derived about their spatial distribution and their motional behaviour in the human tissue. If the applied field is inhomogeneous, the particles will be attracted towards the steepest gradient and may be kept from moving in a blood stream. In this way the particles can be forced to accumulate in a targeted region of the body, e.g. in a tumour. The therapeutic concept of magnetic drug targeting (MDT) where the particles serve as carriers of an anti-cancer drug makes use of this behaviour. In the MDT approach the drug release and its deleterious action is focussed on the tumour and unwanted systemic side effects are reduced [19].

Yet another way to utilise magnetic nanoparticles for confining the therapy to pathological tissue is magnetic thermoablation [13]. In this approach, an alternating magnetic field is applied, so that static action on the particles is averaged out and cancelled. But what remains is a thermal impact as a result of dissipated energy that is mediated via the nanoparticles. If the temperature is raised above certain critical values, the cells die due to the apoptosis mechanism or are immediately destroyed by coagulation. By accumulating magnetic nanoparticles in the limited region of a tumour the temperature increase can be focussed so that, again, unwanted side effects on the healthy tissue are avoided or at least reduced.

High gradient magnetic separation in body fluids like blood is one of earliest but still emerging biomedical applications of magnetic particles [22]. Therefore, we find it appropriate to start this topical issue with a review article on this technology [10] before we address in-vivo applications of magnetic nanoparticles. Magnetic nanoparticles that are used for magnetic drug targeting and thermoablation need to have physical properties that make them particularly suited for their destined function, i.e. they have to be designed in a way so that they perform best as a drug carrier or a heat dissipater [6], respectively. These physical properties have to be characterised by sophisticated measurement techniques in-vitro [16] as well as in a model simulating the in-vivo situation [12]. With this background methodical and experimental studies can provide a deeper understanding of the mechanisms underlying magnetic drug targeting [20, 21] and thermoablation [26].

In order to assess and control the efficacy of these therapeutic approaches, one needs to monitor the spatial distribution of the magnetic particles quantitatively. At first sight, magnetic resonance imaging which visualises magnetic particles via their local impact on the nuclear magnetic relaxation time seems to be the appropriate tool for this purpose [28]. However, it is difficult to derive quantitative information from such data. Here, spatially resolved magnetic measurement techniques such as magnetorelaxometry and ac-susceptometry may offer an alternative. These techniques make directly use of the superparamagnetism of the particles to obtain quantitative information on their distribution in the tissue. Such methods may be useful for therapy control [9, 16] as well as for the general diagnosis and detection of cancerous tissue [4]. Note that also MPI has the potential to provide such quantitative information with outstanding sensitivity and resolution. While currently a lot of effort in MPI research is devoted to optimising magnetic particles as tracers, it might be worthwhile to foster research for developing MPI technology towards a quantitative and sensitive imaging tool for particles that are optimised with respect to their application in therapy rather than to their imaging performance.