Encapsulation of Iron Oxide Nanoparticles into Red Blood Cells as a Potential Contrast Agent for Magnetic Particle Imaging

Abstract

When magnetic nanoparticles (MNPs) are used as a contrast agent for magnetic particle imaging (MPI), they are rapidly excreted during systemic circulation by the reticuloendothelial system such as Kupffer cells in the liver. Therefore, when considering clinical applications of MPI such as long-term monitoring of cardiovascular diseases, increasing the blood circulation time of MNPs by encapsulating the MNPs into actual cells such as red blood cells (RBCs) as a carrier may be practical. The purpose of this study was to create a biocompatible tracer for MPI by encapsulating MNPs (Resovist ®) into RBCs, and to investigate the effect of the encapsulating procedure on the properties of the RBCs loaded with MNPs (L-RBCs). MNPs were encapsulated into RBCs by the hypotonic dialysis method using a hypotonic buffer solution at three different osmotic pressures. Transmission (TEM) and scanning electron microscopic (SEM) images of the L-RBCs were obtained, and the saturation magnetic moment (Ms) was measured using vibrating sample magnetometry (VSM). From the response to a permanent magnet, the findings on TEM images, and the Ms values measured by VSM, we confirmed that RBCs were successfully loaded with MNPs using the hypotonic dialysis method. When the osmotic pressure was 80 mOsm, MNPs were not retained sufficiently inside the RBCs but were adhered to the membrane surface (TEM images), and RBCs lost their biconcave disc shape and shrunk after resealing (SEM images). At 160 mOsm, the Ms value was much lower than those at 80 and 120 mOsm. At 120 mOsm, the shape of RBCs was preserved (SEM images) and the Ms value was the highest when 0.2 ml (5.6 mg of Fe) of Resovist ® was added to the dialysis tube for loading. In conclusion, we successfully encapsulated MNPs into RBCs using the hypotonic dialysis method. Our results suggest that an osmotic pressure of 120 mOsm is optimal for encapsulating MNPs into RBCs using the hypotonic dialysis method.

Interaction of Nanoparticles with Blood Components and Associated Pathophysiological Effects

“…This strategy is based on temporarily opening pores in the membrane of erythrocytes, easily transporting drugs and ensuring that the latter can stay within these cells once the pores have closed [33]. One of the main uses for this system is the delivery of contrast agents contained within superparamagnetic iron oxide (SPIO) nanoparticles, ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles, very small superparamagnetic iron oxide (VSPIO) nanoparticles, and monocrystalline iron oxide nanocompound (MION) particles, which are already registered and approved for use in the United States and Europe [34]. These have been successfully employed for magnetic particle inspection (MPI) techniques involving the imaging of vessels or structures filled with blood, both during interventions and when monitoring long-term cardiovascular diseases [35].…”

Magnetic particle imaging: tracer development and the biomedical applications of a radiation-free, sensitive, and quantitative imaging modality

“…An alternative approach to increasing circulation times includes entrapping the SPIONs into human red blood cells (RBCs). 222 Through nuclear magnetic resonance measurements, such loaded RBCs were demonstrated to circulate for over 12 days in mouse models before an obvious reduction in concentration could be detected. 223 For RBCs loaded with Resovist, transmission electron microscopy images show that the particles have a spatially uniform distribution within the cells, without any discernible indication of particle aggregation.…”

Magnetic Fluid Hyperthermia Based on Magnetic Nanoparticles: Physical Characteristics, Historical Perspective, Clinical Trials, Technological Challenges, and Recent Advances

“…[ 429 ] MPI is a safe, radiation‐free scanning probe, in contrast to CT scanning and nuclear imaging platforms such as PET and SPECT that utilize ionizing radiation of X‐ray, positrons and γ rays. This http://distinctive assemblage of features has rendered MPI with a plethora of applications such as angiography, [ 430 ] brain perfusion, [ 431 ] cancer detection, [ 426 a] gut bleed detection, [ 432 ] stem cell tracking, [ 433 ] cardiovascular, and disease monitoring. [ 434 ]…”