Dextran-coated Superparamagnetic Iron Oxide Particles Research Articles

Factors regulating macrophage endocytosis of nanoparticles: implications for targeted magnetic resonance plaque imaging

Background: The presence of activated macrophages (M∅) is an early and consistent marker of the inflammatory nature of atherosclerotic disease. Dextran-coated superparamagnetic iron oxide particles (SPIO) are avidly endocytosed. These particles have a strong effect on magnetic resonance signal and have been proposed as a non-invasive probe for the presence of early non-occlusive atherosclerotic disease. We describe the extent to which endogenous and exogenous factors regulate M∅ uptake of SPIO particles. Methods and results: Cultured murine M∅-like cells (J744A.1) incubated with SPIO (0, 11.2, 112.0 and 1120 μg Fe/ml) demonstrated significantly reduced SPIO uptake when pretreated with lovastatin to 61% ( P < 0.001) and 43% ( P = 0.02) of control at 1.0 μM and 17.5 μM lovastatin respectively. Interferon-gamma (IFN-γ, 1000 U/ml) increased SPIO uptake to 163% of control, P < 0.05. Interleukin-4 (IL-4, 40 ng/ml) also increased uptake (178% of control, P < 0.04). In cells incubated with SPIO in the absence of serum proteins, SPIO uptake fell to 57% of control ( P < 0.001). Conclusions: Uptake of SPIO by activated M∅ is regulated by endogenous cytokines and serum components as well and exogenous lovastatin. Thus, MRI signal changes after SPIO administration may reflect M∅ phagocytic capacity as well as M∅ presence.

Magnetic resonance imaging of transplanted oligodendrocyte precursors in the rat brain.

The lack of any markers for oligodendrocyte precursors that can be visualized within the intact CNS is a significant barrier to trials of transplantation of these cells which aim to enhance remyelination in multiple sclerosis. We have therefore asked whether dextran-coated superparamagnetic iron oxide (SPIO) can be used to label cells prior to transplantation and then visualized within the brain using MRI. We have shown that an oligodendrocyte precursor cell line CG-4 will take up dextran-coated SPIO particles in vitro. The label remains within the cells after transplantation into adult rat brain, as assessed by electron microscopy, and is visible by MRI as a reduction in signal intensity at the transplant site at both 1 and 7 days after surgery. We conclude that MRI detection of SPIO-labelled cells represents a promising and novel approach to the analysis of oligodendroglial cell behaviour following transplantation that has very significant advantages over currently available methods.

Detection of Single Mammalian Cells by High-Resolution Magnetic Resonance Imaging

This study reports the detection of single mammalian cells, specifically T cells (T lymphocytes) labeled with dextran-coated superparamagnetic iron oxide particles, using magnetic resonance microscopy. Size amplification due to sequestration of the superparamagnetic particles in vacuoles enhances contrast in localized areas in high-resolution magnetic resonance imaging. Magnetic resonance images of samples containing differing concentrations of T cells embedded in 3% gelatin show a number of dark regions due to the superparamagnetic iron oxide particles, consistent with the number predicted by transmission electron microscopy. Colabeling of T cell samples with a fluorescent dye leads to strong correlations between magnetic resonance and fluorescence microscopic images, showing the presence of the superparamagnetic iron oxide particles at the cell site. This result lays the foundation for our approach to tracking the movement of a specific cell type in live animals and humans.