Carboxydextran‐coated superparamagnetic iron oxide nanoparticles affect the fate of Kupffer cells and macrophages

Magnetic nanoparticles are often used for the imaging of liver tumors and atherosclerotic plaques as well as for targeted drug delivery. However, the fate of polymer‐coated iron oxide nanoparticles and their impact on cell functions are not well understood. Upon intravenous injection into mice, carboxydextran‐coated superparamagnetic iron oxide nanoparticles (SPIO) were rapidly incorporation into Kupffer cells, the hepatic macrophages, where they triggered delayed apoptosis and subsequent Kupffer cell depletion. Confocal microscopy of macrophages treated in vitro with SPIO revealed that the internalized SPIO were confined to lysosomal vesicles, where they colocalized with α‐glucosidase. Both, macrophages and recombinant α‐glucosidase degraded the carboxydextran shell of SPIO in a time‐dependent manner. After uncoating, the unprotected iron oxide core triggered increased ROS production leading to sustained JNK activation. The proinflammatory cytokine TNF‐α increased the apoptosis rate, the ROS production and the JNK activation elicited by SPIO. Notably, the SPIO‐induced apoptosis of Kupffer cells could be abolished by treatment of the mice with the radical scavenger edaravone. Thus, SPIO‐based contrast agents are retained for extended time periods by hepatic macrophages, where they elicit delayed cell death that can be blocked by suitable radical scavengers. Funded by the DFG.