Flash nanoprecipitation of hafnia nanoparticle computed tomography contrast agent

Hafnium oxide (hafnia) nanoparticles have recently attracted attention for their application as computed tomography (CT) contrast agents due to their high X-ray attenuation and low cost. Here we employ flash nanoprecipitation (FNP) to formulate hafnia nanoclusters (HNCs) consisting of a core of precipitated individual hafnia nanoparticles and polylactic acid homopolymer and an outer coating of the block copolymer polylactic acid-b-polyethylene glycol (PLA-b-PEG). The HNCs can be produced with controlled hydrodynamic size in the range of 100–300 nm using a simple 3D-printed FNP mixer. The CT performance of the HNCs was evaluated in a pre-clinical small animal scanner and in a clinical scanner. In both systems the HNCs displayed ~1.5× greater contrast compared to the commercial iodinated molecular contrast agent Omnipaque used clinically.