Mannose-poly(ethylene glycol)-linked SPION targeted to antigen presenting cells for magnetic resonance imaging on lymph node

Abstract

The aim of this study is to prepare biocompatible and targetable nanoparticles in lymph nodes (LNs) for lymph node-specific magnetic resonance (MR) imaging. Mannan-coated superparamagnetic iron oxide nanoparticles (SPIONs) (mannan-SPION), carboxylic mannan-coated SPION (CM-SPION), and β-glucan-coated SPION (Glucan-SPION) have been developed to target antigen-presenting cells (APCs), for lymph node detection by MR imaging. In this study, mannose-polyethylene glycol (PEG) was prepared by conjugating D-mannopyranosylphenyl isothiocyanate and amine-PEG-carboxyl. The 3-aminopropyltriethoxysilane (APTES)-activated SPION and the mannose-PEG were cross-linked to produce mannose-PEG-linked SPION (Mannose-PEG-SPION). Mannose-PEG-SPION carrying mannose on the surface were assumed efficient at targeting APCs through the specific interactions of the mannose tethered on the Mannose-PEG-SPION and the mannose receptors on the antigen presenting cells. The hydrophilic PEG corona layer in the Mannose-PEG-SPION could be prevented from aggregation during the systemic circulation with accompanying enhanced specificity and minimized systemic toxicity. The accumulation of SPION in the lymph nodes led to increased negative enhancement in the MR images. In the in vivo study, rats were injected intravenously with Mannose-PEG-SPION and PEG-SPION, as a control and then tracked by MR imaging after 1 h, 2 h, 3 h, and 24 h. MR imaging on lymph nodes clearly revealed the preferential uptake of Mannose-PEG-SPION in immune cell-rich lymph nodes. The predominant accumulation of Mannose-PEG-SPION in the lymph nodes was also confirmed by Prussian blue staining. Based on these results, Mannose-PEG-SPION shows great potential for lymph node-specific MR imaging.