Physicochemical Stability and Protein Corona Profiling on the Interaction of Iron Oxide Nanoparticles with Human Tear

Abstract

The integration of nanotechnology into ophthalmology represents a promising frontier for the development of precision diagnostics and therapeutics aimed at enhancing ocular health. While the systemic interactions of iron oxide nanoparticles (IONPs) with blood plasma have been extensively studied, their biomolecular interactions within the ocular environment, particularly in tear fluid, remain largely unexplored. In this study, we comprehensively investigate the physicochemical behaviour and proteomic corona profiles of IONPs upon exposure to human tear. Dynamic light scattering (DLS) revealed a modest increase in hydrodynamic diameter from ~115±3.3 nm to ~139±0.7 nm, accompanied by reduction in the zeta potential (ZP) from ~ −36±1.7 mV to ~ −29±0.7 mV, indicating protein adsorption. Proteomic profiling via liquid chromatography–mass spectrometry (LC-MS/MS) identified 25 out of 91 native tear proteins selectively adsorbed onto the IONPs. Bioinformatic analysis revealed an enriched corona composed of Lysozyme C, Lactotransferrin, Mammaglobin B, Lipocalin-1, keratins, immunoglobulins, opiorphin propeptide, Keratin II, Protein S100 and mesothelin proteins implicated in bacteriolysis, iron transport, transcriptional regulation, immune response, cytoskeleton, tissue integrity, nucleotide binding, inflammation regulation, skin tissue formation, endogenous inhibition, microbiome homeostasis and signal transduction. These findings provide the first in-depth molecular dynamics of the ocular nano–bio interface, emphasizing the critical influence of tear composition on nanomagnet behaviour. Our results highlight how tear-specific protein corona formation redefines the physicochemical identity of IONPs within the ocular environment and provide a foundational framework for considering how corona-modified nanomagnets may behave in future magnetically guided ocular therapeutics.