Comparison of Methods for Surface Modification of Barium Titanate Nanoparticles for Aqueous Dispersibility: Towards Biomedical Utilization of Perovskite Oxides.

Colloidal perovskite barium titanate (BaTiO3, or BT) nanoparticles (NPs), conventionally used for applications in electronics, can also be considered for their potential as nanocarriers for biomedical imaging and therapy. Biocompatible NPs containing high Z elements present options for extending resolution and sensitivity of computed tomography (CT) techniques. NPs of BT produced by traditional solid state methods tend to have broad size distributions and poor dispersibility in aqueous media. Furthermore, uncoated BT NPs can be cytotoxic due to the leaching of the heavy metal ion, Ba2+. To overcome these challenges, we developed and compared three approaches for surface modification of gel collection synthesized BT NPs (8 nm) to improve their aqueous stability and dispersibility. The first approach was to coat the surface of BT with a single layer of citrate via molecular adsorption. The citrate capped BT NPs exhibited extremely high aqueous dispersibility and a small hydrodynamic size (11 nm). Although the high dispersibility was found to be pH dependent, such aqueous stability sufficiently enabled a feasibility analysis of BT NPs as CT contrast agents. The second approach, a core/shell design, aimed to encapsulate BT nanoaggregates (BTNA) with a silica layer using a modified Stober method. A cluster of 7-20 NPs coated with a thick layer (20-100 nm) of SiO2 was routinely observed, producing larger nanoparticles in the 100-200 nm range. A third approach was developed, combining the best features of the other two, utilizing a reverse-microemulsion method to encapsulate a single BT core within a thin (10 nm) silica skin layer. These BT encapsulates (BT@SiO2) had a particle size of 29 nm. The -OH groups on the silica layer readily enabled surface PEGylation, allowing the NPs to remain highly stable in saline solutions. We further demonstrate that these BT@SiO2-PEG NPs might serve as contrast agents for in vivo CT imaging.