A role for c‐Jun N‐terminal kinases in apoptosis triggered in human macrophages by carboxydextran‐coated superparamagnetic iron oxide nanoparticles

Abstract

Superparamagnetic iron oxide nanoparticles are widely used for cell labeling and as diagnostic contrast media. The aim of this study was to investigate how carboxydextran‐coated superparamagnetic iron oxide (SPIO) and ultrasmall superparamagnetic iron oxide (USPIO) nanosized particles used for magnetic resonance imaging might affect signaling and functions of human macrophages. Within 1 h, both SPIO and USPIO were rapidly taken up by macrophages leading to increased intracellular iron contents. One day after treatment, most nanoparticles were localized within the lysosomal compartment. Prolonged exposure of the macrophages to SPIO and USPIO led to a significantly enhanced production of reactive oxygen species associated with a long‐lasting activation of JNK kinases and induction of apoptosis as measured by surface expression of phosphatidylserine and caspase 3 activation. USPIO elicited a more pronounced cytotoxicity than SPIO. Treatment of macrophages with Trolox® or N‐acetyl‐L‐cysteine, two strucurally different scavengers of reactive oxygen species, or with the JNK inhibitor V abolished the JNK activation as well as the cytotoxicity caused by the iron oxide nanoparticles. These data indicate that nanosized contrast media hamper macrophage function, an effect that can be antagonized with suitable oxygen radical scavengers. This work was supported by the DFG.