Immune cells-specific delivery of mannan-coated superparamagnetic iron oxide nanoparticles for the detection of metastatic lymph node

Abstract

Detection of lymph node (LN) metastasis by magnetic resonance imaging (MRI) has obtained clinical significance for treating cancer patients. LN metastasis often happens through regional lymphatic system, leading to distal tumor formation including lungs, liver and bones. Successful imaging of small and microscopic LN metastasis provides the helpful information in deciding the therapeutic option of cancer. Mannan is a water-soluble polysaccharide having high content of D-mannose residues which can be recognized by mannose receptors on activated macrophages and dendritic cells. Mannan-coated superparamagnetic iron oxide nanoparticles (Mannan-SPION) were developed to be specifically delivered to immune cells in lymph node by receptor-mediated endocytosis. Mannan-SPION was proven to be suitable for MR imaging due to small size, excellent stability in ferrofluid, and low cytotoxicity. From the Prussian blue staining, Mannan-SPION was showed their ability to be taken up by immune cells such as macrophage and dendritic cell. In addition mannan-SPION exhibited enhanced targeted delivery efficiency to macrophages in lymph nodes in vivo compared with PVA-SPION. Especially, LN enhancement of Mannan-SPION on MRI was dramatically increased at the later stage after intravenous injection compared with PVA-SPION control, indicative of the potential to successfully detect micrometastasis in LN.