Though the concepts of magnetic fluid hyperthermia (MFH) were originally proposed over 50 years ago, the technique has yet to be successfully translated into routine clinical application. Significant challenges must be addressed if the field is to progress and realise its potential as an option for treatment of diseases such as cancer. These challenges include determining the optimum fields and frequencies that maximise the effectiveness of MFH without significant detrimental off-target effects on healthy tissue, achieving sufficient concentrations of magnetic nanoparticles (MNPs) within the target tumour, and developing a better mechanistic understanding of MNP-mediated energy deposition and its effects on cells and tissue. On the other hand, emerging experimental evidence indicates that local thermal effects indeed occur in the vicinity of energy-dissipating MNPs. These findings point to the opportunity of engineering MNPs for the selective destruction of cells and/or intracellular structures without the need for a macroscopic tissue temperature rise, in what we here call magnetically mediated energy delivery (MagMED).

Feraheme, is a recently FDA-cleared superparamagnetic iron oxide nanoparticle (SPION)-based MRI contrast agent that is also employed in the treatment of iron deficiency anemia. Feraheme nanoparticles have a hydrodynamic diameter of 30 nm and consist of iron oxide crystallites complexed with a low molecular weight, semi-synthetic carbohydrate. These features are attractive for other potential biomedical applications such as magnetic fluid hyperthermia (MFH), since the carboxylated polymer coating affords functionalization of the particle surface and the size allows for accumulation in highly vascularized tumors via the enhanced permeability and retention effect. This work presents morphological and magnetic characterization of Feraheme by transmission electron microscopy (TEM), Energy dispersive X-ray spectroscopy (EDX), and superconducting quantum interference device (SQUID) magnetometry. Additionally, the results of an initial evaluation of the suitability of Feraheme for MFH applications are described, and the data indicate the particles possess promising properties for this application.

Abstract

Goal This paper investigates the practicality of using a small, permanent magnet to capture magnetic particles out of high-viscosity biological fluids, such as synovial fluid. Methods Numerical simulations are used to predict the trajectory of magnetic particles toward the permanent magnet. The simulations are used to determine a “collection volume” with a time-dependent size and shape, which determines the number of particles that can be captured from the fluid in a given amount of time. Results The viscosity of the fluid strongly influences the velocity of the magnetic particles towards the magnet, hence the collection volume after a given time. In regards to the design of the magnet, the overall size is shown to most strongly influence the collection volume in comparison to the magnet shape or aspect ratio. Conclusion Numerical results showed good agreement with in vitro experimental magnetic collection results. Significance In the long-term, this work aims to facilitate optimization of the collection of magnetic particle-biomarker conjugates from high-viscosity biological fluids without the need to remove the fluid from a patient.

In this paper, the collection of magnetic particles from synovial fluid using Nd-Fe-B micromagnets is quantitatively studied to determine the influence of fluid viscosity and magnet geometry on the velocity distribution and collection rate. Magnetic capture is validated in highly viscous fluids, such as bovine synovial fluid (η ~ 1 Pa·s). A first-order theoretical model has been developed to predict the particle motion, as well as a numerical multiphysics model. Both models exhibit good agreement with in vitro experimental magnetic collection results. The velocity of the magnetic particles is shown to be inversely proportional to fluid viscosity, and two magnetic structures are compared in term of collection efficiency: a cylindrical Nd-Fe-B permanent magnet and a laser-machined conical Nd-Fe-B permanent magnet.