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

Background: The presence of activated macrophages (MO) 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 MO uptake of SPIO particles. Methods and results: Cultured murine MO-like cells (J744A.1) incubated with SPIO (0. 11.2. 112.0 and 1120 121 mug Fe/ml) demostrated significantly reduced SPIO uptake when pretreated with lovastatin to 61% (P < 0.001) and 43% (P = 0.02) of control at 1.0 muM and 17.5 muM lovastatin respectively. Interferon-gamma (IFN-gamma, 1000 U/ml) increased SPIO uptake to 163%. of control. P < 0.05. Interleukin-4 (IL-4. 40ng/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 MO is regulated by endogenous cytokines and serum components as well I and exogenous lovastatin. Thus, MRI signal changes after SPIO administration may reflect MO phagocytic.,tic capacity, as well as Mtheta presence. (C) 2004 Elsevier Ireland Ltd. All rights reserved.