Physical characterization and in vivo organ distribution of coated iron oxide nanoparticles.

Citrate-stabilized iron oxide magnetic nanoparticles (MNPs) were coated with one of carboxymethyl dextran (CM-dextran), polyethylene glycol-polyethylene imine (PEG-PEI), methoxy-PEG-phosphate+rutin, or dextran. They were characterized for size, zeta potential, hysteresis heating in an alternating magnetic field, dynamic magnetic susceptibility, and examined for their distribution in mouse organs following intravenous delivery. Except for PEG-PEI-coated nanoparticles, all coated nanoparticles had a negative zeta potential at physiological pH. Nanoparticle sizing by dynamic light scattering revealed an increased nanoparticle hydrodynamic diameter upon coating. Magnetic hysteresis heating changed little with coating; however, the larger particles demonstrated significant shifts of the peak of complex magnetic susceptibility to lower frequency. 48 hours following intravenous injection of nanoparticles, mice were sacrificed and tissues were collected to measure iron concentration. Iron deposition from nanoparticles possessing a negative surface potential was observed to have highest accumulation in livers and spleens. In contrast, iron deposition from positively charged PEG-PEI-coated nanoparticles was observed to have highest concentration in lungs. These preliminary results suggest a complex interplay between nanoparticle size and charge determines organ distribution of systemically-delivered iron oxide magnetic nanoparticles.

Method to reduce non-specific tissue heating of small animals in solenoid coils.

PURPOSE: Solenoid coils that generate time-varying or alternating magnetic fields (AMFs) are used in biomedical devices for research, imaging and therapy. Interactions of AMF and tissue produce eddy currents that deposit power within tissue, thus limiting effectiveness and safety. We aim to develop methods that minimise excess heating of mice exposed to AMFs for cancer therapy experiments. MATERIALS AND METHODS: Numerical and experimental data were obtained to characterise thermal management properties of water using a continuous, custom water jacket in a four-turn simple solenoid. Theoretical data were obtained with method-of-moments (MoM) numerical field calculations and finite element method (FEM) thermal simulations. Experimental data were obtained from gel phantoms and mice exposed to AMFs having amplitude >50 kA/m and frequency of 160 kHz. RESULTS: Water has a high specific heat and thermal conductivity, is diamagnetic, polar, and nearly transparent to magnetic fields. We report at least a two-fold reduction of temperature increase from gel phantom and animal models when a continuous layer of circulating water was placed between the sample and solenoid, compared with no water. Thermal simulations indicate the superior efficiency in thermal management by the developed continuous single chamber cooling system over a double chamber non-continuous system. Further reductions of heating were obtained by regulating water temperature and flow for active cooling. CONCLUSIONS: These results demonstrate the potential value of a contiguous layer of circulating water to permit sustained exposure to high intensity alternating magnetic fields at this frequency for research using small animal models exposed to AMFs.

Preliminary study of injury from heating systemically delivered, nontargeted dextran-superparamagnetic iron oxide nanoparticles in mice.

AIM: To assess the potential for injury to normal tissues in mice due to heating systemically delivered magnetic nanoparticles in an alternating magnetic field (AMF). MATERIALS & METHODS: Twenty three male nude mice received intravenous injections of dextran-superparamagnetic iron oxide nanoparticles on days 1-3. On day 6, they were exposed to AMF. On day 7, blood, liver and spleen were harvested and analyzed. RESULTS: Iron deposits were detected in the liver and spleen. Mice that had received a high-particle dose and a high AMF experienced increased mortality, elevated liver enzymes and significant liver and spleen necrosis. Mice treated with low-dose superparamagnetic iron oxide nanoparticles and a low AMF survived, but had elevated enzyme levels and local necrosis in the spleen. CONCLUSION: Magnetic nanoparticles producing only modest heat output can cause damage, and even death, when sequestered in sufficient concentrations. Dextran-superparamagnetic iron oxide nanoparticles are deposited in the liver and spleen, making these the sites of potential toxicity. Original submitted 16 August 2011; Revised submitted 21 March 2012; Published online 26 July 2012.

Modified Solenoid Coil That Efficiently Produces High Amplitude AC Magnetic Fields With Enhanced Uniformity for Biomedical Applications.

In this paper, we describe a modified solenoid coil that efficiently generates high amplitude alternating magnetic fields (AMF) having field uniformity (≤10%) within a 125-cm3 volume of interest. Two-dimensional finite element analysis (2D-FEA) was used to design a coil generating a targeted peak AMF amplitude along the coil axis of ~100 kA/m (peak-to-peak) at a frequency of 150 kHz while maintaining field uniformity to >90% of peak for a specified volume. This field uniformity was realized by forming the turns from cylindrical sections of copper plate and by adding flux concentrating rings to both ends of the coil. Following construction, the field profile along the axes of the coil was measured. An axial peak field value of 95.8 ± 0.4 kA/m was measured with 650 V applied to the coil and was consistent with the calculated results. The region of axial field uniformity, defined as the distance over which field ≥90% of peak, was also consistent with the simulated results. We describe the utility of such a device for calorimetric measurement of nanoparticle heating for cancer therapy and for magnetic fluid hyperthermia in small animal models of human cancer.

A nanotube based electron microbeam cellular irradiator for radiobiology research.

A prototype cellular irradiator utilizing a carbon nanotube (CNT) based field emission electron source has been developed for microscopic image-guided cellular region irradiation. The CNT cellular irradiation system has shown great potential to be a high temporal and spatial resolution research tool to enable researchers to gain a better understanding of the intricate cellular and intercellular microprocesses occurring following radiation deposition, which is essential to improving radiotherapy cancer treatment outcomes. In this paper, initial results of the system development are reported. The relationship between field emission current, the dose rate, and the dose distribution has been investigated. A beam size of 23 mum has been achieved with variable dose rates of 1-100 Gy/s, and the system dosimetry has been measured using a radiochromic film. Cell irradiation has been demonstrated by the visualization of H2AX phosphorylation at DNA double-strand break sites following irradiation in a rat fibroblast cell monolayer. The prototype single beam cellular irradiator is a preliminary step to a multipixel cell irradiator that is under development.