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 β-glucan with an immune cell-specific (1,3)-β-d-glucan receptor or Dectin-1 receptor. In this study, superparamagnetic iron oxide nanoparticles (SPIONs) were coated with β-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 β-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.