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

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. 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). 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.