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The aim of this study was to assess a novel lactose functionalized magnetoliposomes (MLs) as an MR contrast agent to target hepatocytes as well as to evaluate the targeting ability of MLs for in vivo applications. In the present work, 17 nm sized iron oxide cores functionalized with anionic MLs bearing lactose moieties were used for targeting the asialoglycoprotein receptor (ASGP-r), which is highly expressed in hepatocytes. Non-functionalized anionic MLs were tested as negative controls. The size distribution of lactose and anionic MLs was determined by transmission electron microscopy (TEM) and dynamic light scattering (DLS). After intravenous administration of both MLs, contrast enhancement in the liver was observed by magnetic resonance imaging (MRI). Label retention was monitored non-invasively by MRI and validated with Prussian blue staining and TEM for up to eight days post MLs administration. Although the MRI signal intensity did not show significant differences between functionalized and non-functionalized particles, iron-specific Prussian blue staining and TEM analysis confirmed the uptake of lactose MLs mainly in hepatocytes. In contrast, non-functionalized anionic MLs were mainly taken up by Kupffer and sinusoidal cells. Target specificity was further confirmed by high-resolution MR imaging of phantoms containing isolated hepatocytes, Kupffer cell (KCs) and hepatic stellate cells (HSCs) fractions. Hypointense signal was observed for hepatocytes isolated from animals which received lactose MLs but not from animals which received anionic MLs. These data demonstrate that galactose-functionalized MLs can be used as a hepatocyte targeting MR contrast agent to potentially aid in the diagnosis of hepatic diseases if the non-specific uptake by KCs is taken into account., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Among the wide variety in iron oxide nanoparticles which are routinely used as magnetic resonance imaging (MRI) contrast agents, magnetoliposomes (MLs) take up a special place. In the present work, the two main types (large and small MLs) are defined and their specific features are commented. For both types of MLs, the flexibility of the lipid coating allows for efficient functionalization, enabling bimodal imaging (e.g., MRI and fluorescence) or the use of MLs as theranostics. These features are especially true for large MLs, where several magnetite cores are encapsulated within a single large liposome, which were found to be highly efficient theranostic agents. By carefully fine-tuning the number of magnetite cores and attaching Gd(3+) -complexes onto the liposomal surface, the large MLs can be efficiently optimized for dynamic MRI. A special type of MLs, biogenic MLs, can also be efficiently used in this regard, with potential applications in cancer treatment and imaging. Small MLs, where the lipid bilayer is immediately attached onto a solid magnetite core, give a very high r2 /r1 ratio. The flexibility of the lipid bilayer allows the incorporation of poly(ethylene glycol)-lipid conjugates to increase blood circulation times and be used as bone marrow contrast agents. Cationic lipids can also be incorporated, leading to high cell uptake and associated strong contrast generation in MRI of implanted cells. Unique for these small MLs is the high resistance the particles exhibit against intracellular degradation compared with dextran- or citrate-coated particles. Additionally, intracellular clustering of the iron oxide cores enhances negative contrast generation and enables longer tracking of labeled cells in time., (Copyright © 2011 John Wiley & Sons, Inc.)