Applicability of Water-LOGSY NMR, Cryo-TEM, and Particle Tracking Analysis to Characterize the Formation of Biocorona on Polymer Nanocarriers

Polymer nanocarriers (PNCs) are increasingly used across diverse applications, including in agricultural practices, which can lead to unintentional exposure of both occupational and general populations. During inhalation, lung fluid (LF) components can form a biocorona on the PNC surface, altering their behavior and potentially influencing their ability to cross biological barriers. Determining whether a biocorona forms under specific conditions is technically challenging, and the absence of standardized approaches limits the safety assessment of PNC-containing products. This study evaluates a combined analytical strategy for biocorona screening in lung fluids, using a nuclear magnetic resonance-based water ligand observed via gradient spectroscopy (water-LOGSY NMR), cryo-transmission electron microscopy (cryo-TEM), and particle tracking analysis. Results obtained for a series of acrylate-based PNCs synthesized at both large and lab-scale are compared to assess whether scale-up affects their properties. Water-LOGSY NMR indicates that the low-molecular-weight components in LF do not interact with acrylate-based PNCs. Although PNC colloidal stability decreases in LF, the lab-scale PNCs remained smaller and more colloidally stable than their commercial counterparts. These differences warn against extrapolating data from lab-scale PNCs to predict the behavior of commercial products. The observed colloidal stability and absence of biocorona formation in LF suggest that, under inhalation exposure, PNCs may exist as nanoparticles for extended periods; therefore, further cellular uptake experiments are recommended to confirm their biological barrier-crossing properties.