Flash Nanoprecipitation of Hafnium Oxide Nanoparticles for Theranostic Applications

Hafnium oxide (hafnia) nanoparticles have demonstrated potential for use in theranostic applications such as computed tomography (CT) and radiotherapy. Thermal composition synthesis methods are of interest for producing hafnia nanoparticles because of their potential to provide better size control and improved cytotoxicity compared to other synthesis techniques. However, thermal composition methods produce particles coated with an organic layer and are hydrophobic. Thus, to be used introduced into the body, it is necessary to prepare the particles using a method that transfers the particles to water while maintaining their stability.

In this study, we investigate flash nanoprecipitation (FNP) as a method of suspending hafnia nanoparticles in water. FNP is a fast, scalable approach to produce composite polymeric nanoparticles through rapid mixing in a multi-inlet vortex mixer. We demonstrate that this technique can be reliably and reproducibly applied to produce composite block copolymer stabilized hafnia nanoparticles in water. Hafnia nanoparticles produced in this work were synthesized through thermal decomposition of hafnia trifluoroacetate in oleylamine. These particles were used to create hafnia nanoparticle clusters (HNCs), featuring a hydrophobic core of hafnia nanoparticles, green fluorophore (3,3′-Dioctadecyloxacarbocyanine perchlorate), and polylactic acid (PLA) stabilized by an outer shell of amphiphilic poly(lactic acid)-b-poly(ethylene glycol) (PLA-b-PEG). These HNCs were evaluated to assess CT performance, stability in cell culture media, and cytotoxicity. From this work we hope to present a novel CT imaging agent with reduced cost and improved biocompatibility to replace current imaging agents.