Targeted delivery of mannan-coated superparamagnetic iron oxide nanoparticles to antigen-presenting cells for magnetic resonance-based diagnosis of metastatic lymph nodes in vivo

Abstract

Metastatic lymph nodes (LN) originate from primary cancer cells that metastasize to the lymphatic system. It is difficult to non-invasively discriminate between metastatic LN and normal LN because of their similarities in size and shape. Magnetic resonance (MR) contrast agents are widely utilized to enhance the image contrast among different tissues. Currently available dextran-based contrast agents are non-specifically internalized by macrophages. Therefore, the aim of this study was to develop mannan-coated superparamagnetic iron oxide nanoparticles (mannan–SPION) for specific delivery to immune cells in LN by receptor-mediated endocytosis for facilitated uptake in the target cells and faster acquisition of MR images. Mannan is a water soluble polysaccharide with a high content of D-mannose residues that can be recognized by mannose receptors on activated macrophages and dendritic cells. Mannan–SPION are proven to be suitable for MRI due to their small size, excellent aqueous stability, and lower cytotoxicity. Mannan–SPION are taken up by antigen-presenting cells such as macrophages and dendritic cells, which could be confirmed by Prussian blue and fluorescent staining. In addition, mannan–SPION exhibit enhanced delivery efficiency in targeting macrophages in LN in vivo compared with polyvinyl alcohol (PVA)–SPION. More specifically, the enhancement of MRI of LN by mannan–SPION increased dramatically during the earlier stages after intravenous injection, compared with PVA–SPION as a control, which indicates the potential for successful and early detection of metastastatic LN.