Lutz Trahms

Targeted delivery of magnetic aerosol droplets to the lung

The inhalation of medical aerosols is widely used for the treatment of lung disorders such as asthma, chronic obstructive pulmonary disease1, cystic fibrosis2, respiratory infection3 and, more recently, lung cancer4. Targeted aerosol delivery to the affected lung tissue may improve therapeutic efficiency and minimize unwanted side effects. Despite enormous progress in optimizing aerosol delivery to the lung, targeted aerosol delivery to specific lung regions other than the airways or the lung periphery has not been adequately achieved to date5,6. Here, we show theoretically by computer-aided simulation, and for the first time experimentally in mice, that targeted aerosol delivery to the lung can be achieved with aerosol droplets comprising superparamagnetic iron oxide nanoparticles—so-called nanomagnetosols—in combination with a target-directed magnetic gradient field. We suggest that nanomagnetosols may be useful for treating localized lung disease, by targeting foci of bacterial infection or tumour nodules.

Drug loaded magnetic nanoparticles for cancer therapy

Magnetic nanoparticles have been investigated for biomedical applications for more than 30 years. In medicine they are used for several approaches such as magnetic cell separation or magnetic resonance imaging (MRI). The development of biocompatible nanosized drug delivery systems for specific targeting of therapeutics is the focus of medical research, especially for the treatment of cancer and diseases of the vascular system. In an experimental cancer model, we performed targeted drug delivery and used magnetic iron oxide nanoparticles, bound to a chemotherapeutic agent, which were attracted to an experimental tumour in rabbits by an external magnetic field (magnetic drug targeting). Complete tumour remission could be achieved. An important advantage of these carriers is the possibility for detecting these nanoparticles after treatment with common imaging techniques (i.e. x-ray-tomography, magnetorelaxometry, magnetic resonance imaging), which can be correlated to histology.

MEG/EEG sources of the 170-ms response to faces are co-localized in the fusiform gyrus.

The 170-ms electrophysiological processing stage (N170 in EEG, M170 in MEG) is considered an important computational step in face processing. Hence its neuronal sources have been modelled in several studies. The current study aimed to specify the relation of the dipolar sources underlying N170 and M170. Whole head EEG and MEG were measured simultaneously during the presentation of unfamiliar faces. An Independent Component Analysis (ICA) was applied to the data prior to localization. N170 and M170 were then modelled with a pair of dipoles in a four-shell ellipse (EEG)/homogeneous sphere (MEG) arranged symmetrically across midline. The dipole locations were projected onto the individual structural MR brain images. Dipoles were localized in fusiform gyri in ten out of eleven individuals for EEG and in seven out of eleven for MEG. N170 and M170 were co-localized in the fusiform gyrus in six individuals. The ICA shifted some of the single-subject dipoles up from cerebellum to fusiform gyrus mainly due to the removal of cardiac activity. The group mean dipole locations were also found in posterior fusiform gyri, and did not differ significantly between EEG and MEG. The result was replicated in a repeated measurement 3 months later.

Determination of the binding reaction between avidin and biotin by relaxation measurements of magnetic nanoparticles

The binding between avidin and biotinylated magnetic iron oxide nanoparticles can be monitored by means of magnetic relaxation measurements. The resultant signal, caused by particle aggregates, has Brownian and Neel components. The time constant and amplitude of Brownian relaxation were determined by a fit algorithm which also yielded Neel amplitudes proportional to the avidin content of the samples.

Aggregation behaviour of magnetic nanoparticle suspensions investigated by magnetorelaxometry

The aggregation behaviour of magnetic nanoparticles (MNP) is a decisive factor for their application in medicine and biotechnology. We extended the moment superposition model developed earlier for describing the Neel relaxation of an ensemble of immobilized particles with a given size distribution by including the Brownian relaxation mechanism. The resulting cluster moment superposition model is used to characterize the aggregation of magnetic nanoparticles in various suspensions in terms of mean cluster size, aggregate fraction, and size dispersion. We found that in stable ferrofluids 50%-80% of larger magnetic nanoparticles are organized in dimers and trimers. The scaling of the relaxation curves with respect to MNP concentration is found to be a sensitive indicator of the tendency of a MNP suspension to form large aggregates, which may limit the biocompatibility of the preparation. Scaling violation was observed in aged water based ferrofluids, and may originate from damaged MNP shells. In biological media such as foetal calf serum, bovine serum albumin, and human serum we observed an aggregation behaviour which reaches a maximum at a specific MNP concentration. We relate this to agglutination of the particles by macromolecular bridges between the nanoparticle shells. Analysis of the scaling behaviour helps to identify the bridging component of the suspension medium that causes agglutination.

SQUID based remanence measurements for immunoassays

The use of fine magnetic particles as labels for antibodies and the measurement of their remanent magnetization for the preparation of immunoassays is presented. Antibodies were coupled with magnetic nanoparticles and samples were prepared by reaction of the magnetically labeled antibodies with their solid phase adsorbed antigen. After exposing the samples to a field of some mT a dc-SQUID system measures the remanent sample magnetization in the absence of an external field. The combination of high moment labels and SQUIDs yields ultrasensitive immunoassays with a wide range of detectable analyte concentrations. In contrast to most standard techniques in our method the detected magnetic signal is specific only for bound reaction partners, thus eliminating the need for separation of unbound components.

Magnetoencephalography with a chip-scale atomic magnetometer

We report on the measurement of somatosensory-evoked and spontaneous magnetoencephalography (MEG) signals with a chip-scale atomic magnetometer (CSAM) based on optical spectroscopy of alkali atoms. The uncooled, fiber-coupled CSAM has a sensitive volume of 0.77 mm3 inside a sensor head of volume 1 cm3 and enabled convenient handling, similar to an electroencephalography (EEG) electrode. When positioned over O1 of a healthy human subject, α-oscillations were observed in the component of the magnetic field perpendicular to the scalp surface. Furthermore, by stimulation at the right wrist of the subject, somatosensory-evoked fields were measured with the sensors placed over C3. Higher noise levels of the CSAM were partly compensated by higher signal amplitudes due to the shorter distance between CSAM and scalp.

Efficient drug-delivery using magnetic nanoparticles — biodistribution and therapeutic effects in tumour bearing rabbits

UNLABELLED To treat tumours efficiently and spare normal tissues, targeted drug delivery is a promising alternative to conventional, systemic administered chemotherapy. Drug-carrying magnetic nanoparticles can be concentrated in tumours by external magnetic fields, preventing the nanomaterial from being cleared by metabolic burden before reaching the tumour. Therefore in Magnetic Drug Targeting (MDT) the favoured mode of application is believed to be intra-arterial. Here, we show that a simple yet versatile magnetic carrier-system (hydrodynamic particles diameter <200nm) accumulates the chemotherapeutic drug mitoxantrone efficiently in tumours. With MDT we observed the following drug accumulations relative to the recovery from all investigated tissues: tumour region: 57.2%, liver: 14.4%, kidneys: 15.2%. Systemic intra-venous application revealed different results: tumour region: 0.7%, liver: 14.4 % and kidneys: 77.8%. The therapeutic outcome was demonstrated by complete tumour remissions and a survival probability of 26.7% (P=0.0075). These results are confirming former pilot experiments and implying a milestone towards clinical studies. FROM THE CLINICAL EDITOR This team of investigators studied drug carrying nanoparticles for magnetic drug targeting (MDT), demonstrating the importance of intra-arterial administration resulting in improved clinical outcomes in the studied animal model compared with intra-venous.

Time domain study of Brownian and Néel relaxation in ferrofluids

Abstract Relaxation of six ferrofluids differing in particle size was studied using a dc SQUID magnetometer. We observed Neel relaxation with nonlinear ln( t ) behaviour in freeze-dried samples and viscosity-dependent Brownian relaxation in glycerol-based dried samples. Investigations of the basic magnetic parameters, complex susceptibility and remanence complement the time-dependent measurements.

How the size distribution of magnetic nanoparticles determines their magnetic particle imaging performance

Spatial and temporal resolution of magnetic particle imaging (MPI), a powerful technique for biomedical imaging, depends crucially on the magnetic properties of the magnetic nanoparticle (MNP) tracer. The authors establish the relation of the static and the dynamic magnetization behavior of various MNP preparations to their MPI performance. While MNPs with a mean diameter of 6 nm achieve only 0.2% of the theoretical maximum amplitude of the third harmonic (at 25 kA/m drive field strength), those with 19 nm diameter attain 57%. The good performance of Resovist, a clinically approved contrast agent for magnetic resonance imaging, is explained by the presence of MNP aggregates.