Highly biocompatible multifunctional nanocomposites consisting of monodisperse manganese oxide nanoparticles with luminescent silica shells were synthesized by a combination of w/o-microemulsion techniques and common sol-gel procedures. The nanoparticles were characterized by TEM analysis, powder XRD, SQUID magnetometry, FT-IR, UV/vis and fluorescence spectroscopy and dynamic light scattering. Due to the presence of hydrophilic poly(ethylene glycol) (PEG) chains on the SiO 2 surface, the nanocomposites are highly soluble and stable in various aqueous solutions, including physiological saline, buffer solutions and human blood serum. The average number of surface amino groups available for ligand binding on the particles was determined using a colorimetric assay with fluorescein isothiocyanate (FITC). This quantification is crucial for the drug loading capacity of the nanoparticles. SiO 2 encapsulated MnO@SiO 2 nanoparticles were less prone to Mn-leaching compared to nanoparticles coated with a conventional bi-functional dopamine-PEG ligand. The presence of a silica shell did not change the magnetic properties significantly, and therefore, the MnO@SiO 2 nanocomposite particles showed a T 1 contrast with relaxivity values comparable to those of PEGylated MnO nanoparticles. The cytotoxicity of the MnO@SiO 2 -PEG/NH 2 nanoparticles was evaluated using primary cells of the innate immune system with bone marrow-derived polymorphonuclear neutrophils (BM-PMNs) as import phagocytes in the first line of defence against microbial pathogens, and bone marrow-derived dendritic cells (BMDCs), major regulators of the adaptive immunity. MnO@SiO 2 -PEG/NH 2 nanoparticles have an acceptable toxicity profile and do not interact with BMDCs as shown by the lack of activation and uptake.

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MnO nanoparticles (NPs) were surface functionalized by two different approaches, (1) using a dopamine-poly(ethylene glycol) (PEG) (DA-PEG) ligand and (2) by encapsulation within a thin silica shell applying a novel approach. Both MnO@DA-PEG and MnO@SiO 2 NPs exhibited excellent long-term stability in physiological solutions. In addition, the cytotoxic potential of both materials was comparatively low. Furthermore, owing to the magnetic properties of MnO NPs, both MnO@DA-PEG and MnO@SiO 2 lead to a shortening of the longitudinal relaxation time T 1 in MRI. In comparison to the PEGylated MnO NPs, the presence of a thin silica shell led to a greater stability of the MnO core itself by preventing excessive Mn ion leaching into aqueous solution.

MnO nanoparticles were surface modified using two different multifunctional polymers. By introducing a PEG group, the long term stability, MRI applicability and sterile filtration could be greatly improved. Furthermore, PEGylated MnO NPs were less toxic compared to nonPEGylated NPs. The results suggest that these nanoparticles are suitable for in vivo applications.