Immune cell-specific delivery of beta-glucan-coated iron oxide nanoparticles for diagnosing liver metastasis by MR imaging

Glucans are reported to elicit immune responses through activation of macrophages by a specific interaction of beta-glucan with an immune cell-specific (1,3)-beta-D-glucan receptor or Dectin-1 receptor. In this study, superparamagnetic iron oxide nanoparticles (SPIONs) were coated with beta-glucan in order to target the immune cells residing in the metastatic liver as an aid for discriminating metastasized tumor regions from normal hepatic parenchymal tissue. The morphology of prepared beta-glucan-coated SPIONs (Glu-SPIONs) was characterized with dynamic light scattering (DLS) and transmission electron microscopy (TEM). The cytotoxicity of Glu-SPIONs was analyzed and compared to that of dextran- and PVA-coated SPIONs. The uptake of Glu-SPIONs by peritoneal macrophages was also confirmed with Prussian blue staining and MRI phantom tube imaging. The in vivo uptake of Glu-SPIONs in liver and lymph nodes in a metastatic mouse liver model was tracked by MR imaging after the systemic injection. The Glu-SPIONs predominantly accumulated in the macrophages surrounding the metastatic regions of the liver thereby indicating the distribution of tumor cells in the liver. MR imaging of the Glu-SPIONs clearly revealed macro- or micro-metastasized tumor regions throughout the liver, due to the preferential uptake of Glu-SPIONs into macrophages, not tumor cells. The Glu-SPION-accumulating regions were further confirmed with H&E and Prussian blue stainings after tissue sectioning. Based on our study, we propose that Glu-SPIONs can be successfully applied for diagnosing hepatic metastasis. (C) 2011 Elsevier Ltd. All rights reserved.