Competing Colloidal Interactions Govern Polymer Encapsulation of Hydrophobic Iron Oxide Nanoparticles

Control over synthesis conditions is necessary to ensure high loading in polymer-encapsulated iron oxide nanoparticles (P-IONPs) and enable biomedical applications. While flash nanoprecipitation (FNP) is a robust method to fabricate P-IONPs, very little is known regarding the response of hydrophobic IONPs to the change in solvent quality during FNP and its effect on the nature of encapsulation. In this work, we first probe the sizes of oleic acid (OA)-coated IONPs at varying compositions of water (ϕw) in a tetrahydrofuran (THF)-water mixture through time-based dynamic light scattering (DLS) and cryo-electron microscopy. It was found that OA-IONPs existed as large (micron)-sized clusters in THF, which broke into smaller clusters as ϕw in the solvent mixture increased. A free energy model of clustering is presented to describe the competing repulsive and attractive interparticle interactions driving the equilibrium cluster sizes (d*) as a function of ϕw. This effect was further pronounced when an aqueous Tween 80 solution was added to the dispersion, resulting in individually dispersed IONPs at high ϕw. The d* directly influenced the nature of P-IONPs produced using FNP at varying aqueous-to-organic flow rate ratios. Finally, a systematic study was performed to investigate the effects of the concentration of polymer and IONPs, and OA surface coverage on IONPs, on the extent and nature of encapsulation. The findings suggest the key role of competing colloidal interactions in governing the fate of synthesized P-IONPs via FNP. The understanding from this study would enable the rational design of P-IONPs with high, uniform loading for desired applications.