Biocompatible Cobalt Oxide Nanoparticles for X-ray Fluorescence Microscopy

The synthesis of water-soluble nanoparticles is a well-developed field for ferrite-based nanoparticles with the majority consisting of iron oxide or mixed metal iron oxide nanoparticles. However, the synthesis of non-agglomerated non-ferrite metal/metal oxide NPs is not as well established. The synthesis and characterization of uniform 20 nm, biologically compatible cobalt oxide (CoO) nanoparticles (NPs) is described. These nanoparticles have two principle components: 1) a CoO core of suitable size to contain enough cobalt atoms to be visualized by X-ray fluorescence microscopy (XFM) and 2) a robust coating that inhibits NP aggregation as well as renders them water-soluble and biocompatible (i.e. stealth coatings). Stable cobalt oxide NPs are obtained with octadecyl amine coatings as reported by Bhattacharjee. Two strategies for solubilizing these NPs in water were investigated with varying degrees of success. Exchanging the octadecyl amine coating for a nitrodopamine anchored PEG coating yielded the desired water-soluble NPs but in very low yield. Alternately, leaving the octadecyl amine coating on the NP and interdigitating this with a maleic anhydride-vinyl copolymer with different hydrophobic sidechains followed by opening the maleic anhydride ring with amine substituted PEG polymers (the water solubilizing component), yielded the desired water soluble NPS were obtained in good yield. Characterization data for the nanoparticles and the components of the coatings required for bioorthogonal reactions to ligate them with biotargeting agents are also described.