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Colloidal perovskite barium titanate (BaTiO 3 , or BT) nanoparticles (NPs), conventionally used for applications in electronics, can also be considered for their potential as biocompatible computed tomography (CT) contrast agents. 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 because of leaching of the heavy metal ion, Ba 2+ . Here, we present and compare three approaches for surface modification of BT NPs (8 nm) synthesized by the gel collection method to improve their aqueous stability and dispersibility. The first approach produced citrate-capped BT NPs that exhibited extremely high aqueous dispersibility (up to 50 mg/ mL) 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 with a silica layer using a modified Stober method. A cluster of 7−20 NPs coated with a thick layer (20−100 nm) of SiO 2 was routinely observed, producing larger NPs in the 100−200 nm range. A third approach was developed using a reverse-microemulsion method to encapsulate a single BT core within a thin (10 nm) silica layer, with an overall 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 report that the silica-coated BT NPs in both methods exhibited a low level of Ba 2+ leaching (≤3% of total barium in NPs) in phosphate-buffered saline for 48 h compared to the unmodified BT NPs (14.4%).

Targeted radiotherapies maximize cytotoxicity to cancer cells. In this work, we describe the synthesis, characterization, and biodistribution of antibody conjugated gold-coated lanthanide phosphate nanoparticles containing 177 Lu. [ 177 Lu]Lu 0.5 Gd 0.5 (PO 4 )@Au@PEG 800 @Ab nanoparticles combine the radiation resistance of crystalline lanthanide phosphate for stability, the magnetic properties of gadolinium for facile separations, and a gold coating that can be readily functionalized for the attachment of targeting moieties. In contrast to current targeted radiotherapeutic pharmaceuticals, the nanoparticle-antibody conjugate can target and deliver multiple beta radiations to a single biologically relevant receptor. Up to 95% of the injected dose was delivered to the lungs using the monoclonal antibody mAb-201b to target the nanoparticles to thrombomodulin receptors. The 208 keV gamma ray from 177 Lu decay (11%) can be used for SPECT imaging of the radiotherapeutic agent, while the moderate energy beta emitted in the decay can be highly effective in treating metastatic disease.