Unraveling the Structure and Density of the PEG Corona on Upconverting Nanoparticles with SANS

Upconverting nanoparticles (UC-NPs) are unique in their ability to convert near-infrared light into shorter wavelength radiation, presenting valuable opportunities in health and technology. Optimal fluorescence efficiency in UC-NPs requires homogeneous shapes and sizes, which is best achieved through thermal decomposition synthesis using oleic acid (OA) as a surface ligand in organic solvents, thus yielding hydrophobic particles. For biomedical applications, poly(ethylene glycol) (PEG), which forms a stabilizing corona minimizing interactions with proteins and extending blood circulation time, is used to replace OA. However structurally characterizing the PEG layer, while crucial, is challenging due to its low contrast in electron microscopy and Small-Angle X-ray Scattering. To overcome this, our approach uses Small-Angle Neutron Scattering (SANS) with contrast variation of the solvent (H2O/D2O), hence highlighting the PEG layer. Furthermore, multiple contrasts provide model-independent information on the PEG fraction on the particles. This proposal aims to use contrast-variation SANS to probe the thickness, graft density, and configuration of PEG on UC-NPs and detect the presence of residual OA. Our study, part of the EU project Metrology for Innovative NanoTherapeutics (MetrINo-https://metrino.eu), will enhance our understanding of PEGylation in UC-NPs for biomedical applications, and contribute to the development of harmonized measurement and data analysis methods.