Refine
Year of publication
Institute
Has Fulltext
- no (51)
Document Type
- Article (19)
- Part of a Book (9)
- Conference: Meeting Abstract (9)
- Conference Proceeding (6)
- Conference Poster (5)
- Book (1)
- Doctoral Thesis (1)
- Examination Thesis (1)
Keywords
- Frequency mixing magnetic detection (1)
- Hyperthermia (1)
- Iron oxide nanoparticles (1)
- Langevin theory (1)
- MPI (1)
- MRI (1)
- Magnetic nanoparticles (1)
- Micromagnetic simulation (1)
- Monte Carlo method (1)
- Nonequilibrium dynamics (1)
Cardiopulmonary bypass (CPB) is a standard technique for cardiac surgery, but comes with the risk of severe neurological complications (e.g. stroke) caused by embolisms and/or reduced cerebral perfusion. We report on an aortic cannula prototype design (optiCAN) with helical outflow and jet-splitting dispersion tip that could reduce the risk of embolic events and restores cerebral perfusion to 97.5% of physiological flow during CPB in vivo, whereas a commercial curved-tip cannula yields 74.6%. In further in vitro comparison, pressure loss and hemolysis parameters of optiCAN remain unaffected. Results are reproducibly confirmed in silico for an exemplary human aortic anatomy via computational fluid dynamics (CFD) simulations. Based on CFD simulations, we firstly show that optiCAN design improves aortic root washout, which reduces the risk of thromboembolism. Secondly, we identify regions of the aortic intima with increased risk of plaque release by correlating areas of enhanced plaque growth and high wall shear stresses (WSS). From this we propose another easy-to-manufacture cannula design (opti2CAN) that decreases areas burdened by high WSS, while preserving physiological cerebral flow and favorable hemodynamics. With this novel cannula design, we propose a cannulation option to reduce neurological complications and the prevalence of stroke in high-risk patients after CPB.
In the innovative tumor treatment approach of magnetic fluid hyperthermia (MFH), magnetic nanoparticles (MNP) are accumulated at the tumor site and heated in a time-varying magnetic field to substantially damage the tumor (1). This tumor damage depends mainly on the rate and amount of heat delivered via the MNP locally, which is in turn governed by a multitude of variables including the applied field amplitude and frequency, particle size and size distribution. In this study, we compare measured heating rates of MNP with sizes ranging from 21 nm to 28 nm with those obtained from Monte Carlo simulations of non-equilibrium Langevin dynamics to predict particle sizes and field amplitude /frequency settings for optimized MFH within medically safe tolerances. We have synthesized monodisperse iron-oxide MNP via thermal decomposition, coated with poly(ethylene glycol) methyl ether amine (mPEG NH2) as reported in (2). Transmission electron microscopy analysis yielded core sizes (and log-normal distribution width) of 21.9 nm (0.04), 23.1 nm (0.05), 25.3 nm (0.08) and 27.7 nm (0.07). These MNP were subjected to magnetic fields with amplitudes h0 = (6...20) mT/ 0-1 and frequencies f = (176...993) kHz in a magneTherm hyperthermia device (nanoTherics Ltd., Newcastle under Lyme, UK). From the recorded timetemperature curves we calculated the specific loss power (SLP) as a measure of the heating rate: SLP values increased generally with size and frequency (Fig. 1a), as well as with the field amplitude (not shown here). Monte Carlo based stochastic Langevin equation simulations combining Néel and Brownian rotation relaxation and thermal activation (based on (3)) verified this trend (Fig. 1b). Under the assumption of an upper field limitation of f[kHz] · h0[mT/ 0-1] 1758 imposed by medical safety requirements (4), we simulated a heat map based on the parameters obtained from fitting simulation to experiment (Fig. 1c). This map shows maximum SLP values for frequencies f ~ 100 kHz (equivalent to h0 ~ 17.5 mT/ 0-1) at particle sizes of 29 nm and greater. These results can provide a pivotal and integral tool for predicting particle sizes and applied field settings for optimized MFH.
Heating efficiency of magnetic nanoparticles decreases with gradual immobilization in hydrogels
(2019)
Dual frequency magnetic excitation of magnetic nanoparticles (MNP) enables enhanced biosensing applications. This was studied from an experimental and theoretical perspective: nonlinear sum-frequency components of MNP exposed to dual-frequency magnetic excitation were measured as a function of static magnetic offset field. The Langevin model in thermodynamic equilibrium was fitted to the experimental data to derive parameters of the lognormal core size distribution. These parameters were subsequently used as inputs for micromagnetic Monte-Carlo (MC)-simulations. From the hysteresis loops obtained from MC-simulations, sum-frequency components were numerically demodulated and compared with both experiment and Langevin model predictions. From the latter, we derived that approximately 90% of the frequency mixing magnetic response signal is generated by the largest 10% of MNP. We therefore suggest that small particles do not contribute to the frequency mixing signal, which is supported by MC-simulation results. Both theoretical approaches describe the experimental signal shapes well, but with notable differences between experiment and micromagnetic simulations. These deviations could result from Brownian relaxations which are, albeit experimentally inhibited, included in MC-simulation, or (yet unconsidered) cluster-effects of MNP, or inaccurately derived input for MC-simulations, because the largest particles dominate the experimental signal but concurrently do not fulfill the precondition of thermodynamic equilibrium required by Langevin theory.
The heat generated by magnetic nanoparticles (MNP) forms the basis of magnetic fluid hyperthermia (MFH) tumor therapy and arises from MNP magnetic moments relaxing in an alternating magnetic field. In physiological environments MNP strongly interact with cells, binding to their membranes as well as internalizing inside lysosomes, which alters the MNP magnetic relaxation. In the present study, we investigate the heating behavior of MNP in-vitro for different binding states and compare it to the heating of trapped MNP in dedicated hydrogels of different mesh size, mimicking different immobilization states. We used iron-oxide MNP (mean core size 10 nm) with a biocompatible phospholipid coating, referred to as magnetoliposomes (ML), for in-vitro studies, and with citric acid coating (CA-MNP) for studies in hydrogels. All samples were subjected to an AMF (40 kA/m, 270 kHz) for 30 min, and from the recorded time-temperature curve, the specific loss power (SLP) value was calculated. In-vitro experiments were performed with L929 cells, which were incubated for 24 h with 225 μg(Fe)/mL ML dispersed in RPMI cell medium. The results of the SLP values were analyzed regarding the internalized ML amount with respect to ML residuals in RMPI medium and compared to fully immobilized ML after freeze-drying (FD): The SLP value of 10.1 % intracellular ML decreased by 20 %, the SLP value of 100 % intracellular ML decreased by 60 % and that of FD-ML decreased by 70 % (Fig 1a). The influence of gradual immobilization of MNP on the heating was investigated by mixing CA-MNP in low-melting agarose and polyacrylamide hydrogels. In agarose and polyacrylamide gels the mean mesh size can be tuned via the amount of monomers and cross-linkers, respectively, and in this way the state of MNP immobilization is influenced. SLP values decreased by up to 40 % in agarose gels for mesh sizes smaller than the hydrodynamic size dH = 20.6 nm. A comparable decrease was observed in polyacrylamide gels (Fig 1b & c). We attribute this drop in SLP values to a gradual immobilization of MNP trapped in the hydrogels, which blocks particle relaxation and therefore decreases heating efficiency. This agrees very well with the results of the in-vitro measurements. The relative difference in the SLP drop in agarose and polyacrylamide hydrogels for similar mesh sizes might be explained by their gel-specific microstructures, which influence the MNP freedom of movement. For validation of these results, further investigations of the relaxation behavior of such trapped MNP via magnetic particle spectroscopy are currently under progress.
Hyperthermia with the use of magnetic nanoparticles (MNP) is a challenging but most promising approach for cancer therapy. After being magnetically trapped at the tumor site, MNP are heated in alternating magnetic fields (AMF) to approx. 43 °C, which causes tumor cell apoptosis. For an effective and controllable hyperthermia application, two parameters are most important: the amount of internalized MNP in tumor cells and their heating characteristics in AMF. In this study, we evaluated if a sufficient temperature could be achieved by cell internalized MNP heated up in AMF and if cell death could be induced in this way. The heating of pancreatic tumor cell lines MiaPaCa-2 and BxPC-3 loaded with different amounts of selfsynthesized magnetoliposomes nanoparticles (MLs) was measured with a custom-built setup. The MLs consisted of a fluorescent bi-layer of phospholipids and multiple magnetite (Fe3O4) cores with a diameter of (10.0 ± 0.5) nm each. The hydrodynamic diameter of the MLs was (90 ± 5) nm. Cell loading was performed by incubation of tumor cells for up to 24 h at 37 °C in a DMEM cell medium with MLs, which had an iron concentration of 150 μg/mL. Transmission electron microscopy and fluorescence microscopy were used to depict the uptake of MLs into the tumor cells (see Figure). The internalized iron-content per cell was determined with a magnetic particle spectrometer (MPS). After application of AMF for approx. 30 min, cell viability was assessed by clonogenic assay. The cellular uptake of MLs was time-dependent, cell line-specific and saturated: For both MiaPaCa-2 and BxPC-3 cell lines, the MLs cell internalization followed an exponential growth function which saturated after about 24 h cell incubation time at an iron load of (110 ± 6) pg/cell and (30 ± 2) pg/cell, respectively. The time constants of the exponential growth were (7.2 ± 1.4) h and (4.0 ± 0.6) h, respectively. In AMF, cells with the saturated MLs loading reached temperatures of approx. 44 °C and 43.5 °C, which caused the cell survival fraction to drop to approx. one third compared to untreated tumor cells for both MiaPaCa-2 and BxPC-3 cell lines. These results demonstrate the feasibility of hyperthermia in pancreatic cancer treatment by confirming cell death of pancreatic tumor cells at temperatures of approx. 43 °C. Further investigations are planned, which aim for the optimization of MNP dosage in targeting experiments as well as the assessment of incubation times and AMF parameters needed for a successful hyperthermic therapy.
